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Tuberculous meningitis
December 1955
373
Tuberculous Meningitis By S. RUSSELL JAMIESON Castle Hill Hospital, Cottingharn, East Yorkshire This paper is a review of 60 cases of tuberculosis meningitis that have been treated at Castle Hill Hospital, Cottingham, since the introduction of streptomycin in z948. The first series of 35 cases were those admitted up to the end of I95x and they were treated with streptomycin and PAS, and the second series of 25 cases were those admitted after z951 and were treated with streptomycin, PAS, and Isoniazid. On admission all cases were classified as: (I) Early case (E) - fully conscious patient with no focal signs, slight nuchal rigidity but with abnormal cerebrospinal fluid (2). (2) Middle case (M) - fully conscious, but sometimes drowsy and lethargic with nuchal rigiditY and focal signs (I9). (3) Advanced case (A) - unconscious or deeply stuporous patient (39). The diagnosis was confirmed by isolation of the tubercle bacillus from the cerebrospinal fluid in 5 x cases. The 9 from which tubercle bacilli were absent showed other specific signs and symptoms of the disease. The results of treatment were assessed after a survival period of six months from the date of admission and cases were observed up to six years. History of Contact. - A definite history of contact with diagnosed tuberculosis in the home was found in 22 of the 6o cases. Mantoux test was performed in all cases and found to be positive. Radiography. - . Definite abnormalities in the chest x-ray film were seen in 38 of the 6o cases. They comprised (a) a primary complex (usually hilar adenitis with a pulmonary focus) in x6 cases; (b) miliary disease of the lungs in 13 cases; and (c) phthisis in 9 cases. G.S.F. Examination. - The general appearances of the C.S.F., cell count, protein content, chlorides and sugar were estimated monthly along with direct examination for tubercle bacilli and culture on Lowenstein's
medium. If a Mantoux-positive case with no tubercle bacilli on direct examination showed a lymphocytosis with increased protein and lowered sugar and chloride content on two occasions, treatment was begun without further delay. FIRST SERIES Treatment In the first series of 35 cases, all patients were given a six-month course of intramuscular and intrathecal streptomycin combined with oral PAS. The daily dose of intramuscular streptomycin was z gramme and was given to all patients in two twelve-hourly doses of o . 5 gramme. The daily dose of intrathecal streptomycin was zoo rag. for patients of 5 years and over, and 5 ° mg. for those under 5 years. Oral PAS was given in gradually increasing dosage to I8 grammes for patients x2 years and over, 9 grammes for those 5-zI years, and 4-5 grammes for those I - 4 years. PAS was given continuously throughout the patients' stay in hospital in the recommended dosage. O n discharge it was continued as a bacteriostatic agent at a reduced dosage for a further two years. Treatment was given for six days a week, Sunday being a complete rest period. All patients were kept in bed for six months' course of streptomycin treatment. A radiograph of the lungs was taken and full chemical and bacteriological examinations ofthe cerebrospinal fluid were made monthly. Patients were not allowed up until the C.S.F. was normal, and they were kept in hospital for at least one year. Results O f the 35 patients treated, 28 survived and 7 died. O f the 28 survivors, 19 are clinically fit and well, of the remaining 9, 4 are permanently deaf, 3 wear corrective splints for leg deformities and 2 are mentally retarded. Table I shows the details of the 35 cases.
F
F
M
M
F
M
-"8
ix
x4
",
x xo/x',
2
6
48
2o
24/r,0
x6
3
xI 9/x."
x
15 6Do
x3
2
3
4
5
6
7
8
9
xo
IX
Io
x3
x4
x5
x6
z7
F
M
M
M
F
F
M
M
M
M
M
2
x
Sex
Age (years)
Case .No.
7
6
zo
t3
."x
~o
xx
5
x4
x2
z',
---4
28
28
",x
14
x4
History (daj,s)
M
A
M
A
A
M
A
A
A
M
A
M
A
A
A
A
A
Too ill Millary Miliary P.C.
Phthisis o
Uxooo + ,/xooo + x/moo + X/XOOO +
x/moo + Umoo +
+
P.C. o
x/xooo +
P.C.
Miliary
Miliary
o
x/xooo +
x/xooo +
x/xoo
z/moo +
x/moo +
P.C.
+
+
Too ill
x/moo +
x/moo +
+
+
P.C.
//moo +
o
+
+
o
+
o
+
o
o o
+
o
+
+
0
o
o
o
o
0
+
+
+ +
+
o
+
o
Phthisis
//moo +
o
o
Chest x-ray
Direct History exam. of of C.S.F. contact for T.B.
Umooo+ Miliary
Condition on Mantoux admission test
+
+
+
+
q-
+
+
+
+
+
+
0
+
+
+
+
+
Culture of C.S.F. for T.B.
TABLE I. - FIRST SERIES
I6O
5 years
5 years
5 years
5 years
5 years
C.S.F. normal. Full recovery
Recovery. Deafness. C.S.F. normal
Recovery. Mentally retarded. Difficulty in walking. Improving. C.S.F. normal
C.S.F. normal. Full recovery
Recovery. Tuberculous ankle healed
C.S.F. normal. Full recovery
C.S.F. normal. Full recovery
Died
6 years
x26
x55
tuberculous
Recovery. Right hemiplegia, much improved on 58oth day. C.S.F. normal
5 years
x67
slmwed
Relapsed and died 9 months after completion of treatment. P.M. showed tuberculoma of brain
Died
Died. P.M. meningitis
Died
Died
Died
Full recovery. C.S.F. normal. Spu tum negative
Full recovery
Result
5 years
6 days
4~ years
2x days
23 days
x9 days
17 days
x21 days
4 years
5 years
Observation
x6x
z62
x68
x79
6
z(;o
x8
=3
19
x7
I20
14t
x66
Streptomycin treatment (days)
Lrl
t~
r-rrl
C tT~ m 7a (3
tad
Age (years)
2
19 6/to
7
2 .°
x7
5 xi/x.0
23
~ xx/x~
6
18
z4
9/=~
', 6/I-0
2 6/i~
3
x4
8
xo
Case No.
I8
19
~o
~t
.02
.03
.04
.05
.06
27
-08
~9
3°
3t
3°
33
34
35
,/xooo + x/mooo+ =/xoooo+ i/~ooo +
x/xooo +
i1,oooo+ x/1ooo + x/xoooo+ t/x0oo + z/moo +
x/zoooo+ ,/ioooo+ ,/=ooo + xDoooo+ ffIoooo+ x/looo + I/xooo +
M
M
M
A
A
A
A
E
A
M
IVI
M
A
E
M
M
A
7
14
t4
7
x2
8
6
x4
7
14
x4
5
x4
7
ix
x4
xo
Miliary
P.C.
o
P.C.
o
P.C.
P.C.
Miliary
P.C.
P.C.
P.C.
o
o
o
P.C,
o
o
P,C.
Cl,est x-ray
o
+
o
+
o
o
+
o
+
+
o
+
+
o
+
+
o
o
+
o
o
+
o
o
o
o
+
o
+
+
+
+
o
o
o
o
160 x68 t64 x64 x68 x68
o + o + +
4 years
4 years
4 years
4 years
4 years
4 years
Recovery. Deafness. C.S.F. normal
C.S.F. normal. Full recovery
C.S.F. normal. Full recovery
C.S.F. normal. Full recovery
C.S.F. normal. Full recovery
C.S.F. normal. Full recovery
Recovery. Left hemlplegia. Much improved. C.S.F. normal +
6 years
t6o
+
Full recovery'. C.S.F. normal 4 years
Readmitted 6 months after discharge with miliary tuberculosis of lungs. Much improved with 2rid course of dihydrostreptomycin. C.S.F. normal. Deafness
Recovery. Mentally retarded. C.S.F. normal
5 years
C.S.F. normal. Full recovery
6 years
x68
+
4 years
C.S.F. normal. Full recovery
16o
x68
+
4 years
C.S.F. normal. Full recovery
o
i68
+
4 years
C.S.F. normal. Full recovery
C.S.F. normal. Full recovery
Recovery. Deafness. C.S.F. normal
x68
+
4 years
5 years
4 years
x62
+
C.S.F. normal. Full recovery
I7O
x57
+
5 years
C.S.F. normal. Full recovery
+
x6o
+
5 years
Result
x7o
x6o
Observation
0
(days)
+
Streptomycin treatment
C.S.F. for T.B.
of
Culture
P.C. = Primary complex Miliary = Miliary disease of lungs
Direct History exam. of o.f C.S.F. contact for T.B.
M = Middle case A = Advanced ease
,/moo +
Mantoux test
A
IO
E = Early case
M
M
M
M
M
M
F
F
F
F
M
F
F
F
M
M
F
M
Sex
Condition on History (days) admission
tD
rFit
WI
-4 C
t.a"t
ot fD
M M hi F
F
5
~9
2I o9 5 3[I-.q
4 4 5 5
'3 20 2 3]Ia ',
xI ~7 t6
x5 4/I-,,
4
, 6/12
5
6
7 8 9 Io
Ix x2 t3 I.t-
'5
,6 t7 x8
19 2o 2I
22 23
e4
25
4
7
xt 2
x4 x4 ',x
7 6 7
3
5 3° 9 7
to 3° 7 ~o
20
3
5 to 3
Itistory (day~) 8
E Early case
M
F
M F
F F F
F F F
M M M M
F
M
M M F
8 ~x x
..q 3 4
Sex F
Age (years) I7
Case .No. I
+ + + +
x/,ooo +
x/moo +
x/Iooo + x/xooo +
x/xooo + i/Iooo + t/Iooo +
,/moo + I/IOOO+ x/xooo +
x/,ooo +
i/tooo I/*ooo 1]tooo I/tooo
I/xooo + I/,ooo + I/IOOO+ x/iooo +
x/tooo +
,[,ooo +
I/tooo + z/Iooo + l/tooo +
M = Middle case
A
A
A A
A A A
M A A
M
M A A A
A A A A
A
M
A M A
Condition on Alantoux admission test M x/Iooo +
+ o +
o o o o
o
o
+
+
+ + +
+
+
+ + o
+ + + +
+ +
,-[o o
+
q-
+ + o
+
for T.B.
c.s.y.
Culture of
980
9o
9°
~73 21
x4 9x
90 90 90 9° 2I
14 9x
Result
Full recovery Full recovery Full recovery Full recovery Left-sided hemlplegla. N o w full recovery Died. P.M. showed tuberculous meningitis with hydrocephalus Died. Severe bedsores Full recovery Full recovery Full recovery Full recovery Full recovery Full recovery Full recovery Full recovery Full recovery Full recovery Full recovery Full recovery Full recovery Full recovery Deafness, otherwise fit a n d well Died. P.M. showed tuberculous meningitis a n d miliary tuberculosis Died Died. P.M. showed tuberculous meningitis a n d hydrocephalus Miliary = Miliary disease of lungs
598 54 ° 420 2Io 200 200
9° 90 9°
94 93o 900 84 o 776 720 7x6 690 60o
9° 9° 90 9o 90 90 90 9° 9°
x9
x9
1,050 x,o5o 1,020
9° 90
Days of observation I,I IO
Streptomyc~ treatment (days) 9o
P.C. = P r i m a r y complex
+
o
o o o
+ o
o o
+ + +
o o o
o o +
+
+
+
+
o
o
+
o + o
o o o
o
+
:F
o o
for T.B.
contact
o o +
c.s.y,
of
A = A d v a n c e d case
o
Phthisis
Miliary
o
Miliary o Miliary
o O Phthisis
o
Miliary P.C. P.C. Miliary
o o Phthisis lVIiliary
Phthisis
o
o Phthisis Phthisis
Chest x-ray Phthisis
Direct exam. of
tllsto~y
T A B L E II. - SECOND SERIES
,,.o (d-I
-2
rITI
(3
17"1
"-t C
w ",,4
December 1955
T U BERC L E
377
the daily dose and the total dose administered. For example, it has been reported that reTreatment ducing the daily dose of streptomycin from In the second series of 25 cases, patients were 3 grammes to z gramme substantially degiven a three-month course of intra- creased the incidence of vestibular damage muscular and intrathecat streptomycin com- though therapeutic results were in no way bined with oral PAS of the same dosage as impaired. It follows that, though a dose of in the first series. Isoniazid was also given in streptomycin and dihydrostreptomycin toincreasing dosage to zoo mg. t.i.d, for gether will have the same t h e r a p e u t i c patients z2 years and over, and 50 mg. t.i.d. activity as an equivalent dose of either for younger patients. The Isoniazid and antibiotic used alone, if only half as much PAS was given continuously throughout the of each antibiotic is being used there will be patient's stay in hospital in the recommended a reduction in neurotoxic effects because dosage. On discharge both drugs were con- these are different for the two substances. tinued as a bacteriostatic agent, Isoniazid Marked degrees of hearing loss and partial for three months and PAS for a further two deafness form the one serious complication years. Patients were allowed up after comwhich occurs in cases otherwise fit and well pleting their three months' course of strepand the education of the affected patients tomycin and discharged home at the end of would certainly suffer without special educasix months in hospital. tional treatment. Some authorities believe that the deafness Results is due to the tuberculous process and support O f the 25 patients treated, 20 survived and this by the fact that streptomycin has been 5 died. O f these 20 survivors, 19 are clinically extensively used for other forms of tuberfit and well and the remaining one shows culosis and while admitting damage to the permanent deafness. balancing mechanism in the inner ear Table II shows the details of the 2 5 cases. affirm that it is not a cause of deafness when used in the normal dosage. Discussion The occurrence of deafness in cases of During streptomycin - PAS, treatment tuberculous meningitis treated with streprashes, fever, loss of weight, anorexia, tomycin shows considerable variation in vomiting, vertigo, deafness, and albuincidence from place to place and in order minuria occur in varying degrees. With to obtain reliable statistics it would be the exception of deafness, most of these necessary to do objective tests of hearing in symptoms subside when the streptomycin all cases, otherwise cases of high-frequency is stopped. During the past year a comdeafness might easily be missed. bination of streptomycin and dihydroWith Isoniazid, the only serious complicastreptomycin, Dimycin, has been used to tion was the appearance of massive bed sores reduce or eliminate the neurotoxic effects in 2 patients. This was looked upon as a that might develop from using either subnicotinic acid deficiency and all patients stance singly. receiving Isoniazid are also given nicotinic Streptomycin and dihydrostreptomycin acid 5 ° mg. b.i.d. have, for all practical purposes, the same As regards the mental impairment followtherapeutic effect. Both can have a serious effect on the eighth cranial nerve, strep- ing tuberculous meningitis, it is difficult to tomycin affecting primarily vestibular and assess and repeated follow-up examinations dihydrostreptomycin auditory function; ex- are necessary to ascertain whether this is perience has shown that these toxic effects likely to be permanent. (Concluded on page .386) depend to a large degree upon the size of SECOND SERIES
386
T U BERC LE
female patients, who in view of adverse social circumstances cannot look after themselves or cannot be cared for by their relatives. Ever since our unpleasant experience of having to separate a newly arrived elderly immigrant couple, sending the tuberculous husband to a sanatorium and the healthy wife to a home for tile aged, we were convinced of the need to allow couples to live together. The home therefore accepts the healthy marriage partner also. The age of admission has been set at 65 for men and 60 for women, but patients somewhat younger arc also accepted if they are found otherwise suitable. The patients have to be ambulant, not in need of nursing care and able to carry out for themselves the ordinary activities of daily life. Three share a room, married couples have a room to themselves. Apart from recreational activities, nearly all are participating in occupational therapy, make their own beds and take turns in helping in the dining room. The medical team includes a general practitioner, nurses, a social worker, an occupational therapist, a visiting dentist and tuberculosis specialist. Diagnostic facilities allow for x-ray and routine laboratory examinations to be carried out on the spot, while cultures and other special examinations are performed at the laboratory at Beer-Yaacov Hospital. Sick rooms are provided for those suffering from intercurrent illnesses. In case of serious exacerbation of their tuberculous lesion, the patients are admitted to a tuberculosis hospital. Should their social circumstances permit it, the inhabitants might be living in their own homes under Chest Clinic Supervision carrying out the activities of elderly people. The Home for the Aged Tuberculous tries to provide these facilities and at the same time to stimulate the inhabitants to become interested in their own little community, thereby living a fuller life. The H o m e has only been in existence for two and a half years and it is still too early to draw conclusions from our short experience. However, the character of this installation makes its progress a m a t t e r of great interest to us all.
December 195S
Conclusion Faced only five years ago with a task far exceeding existing means; Israel has nevertheless made considerable progress in the rehabilitation and absorption of tuberculous immigrants, whom unselected mass emigration and the wholesale transfer of hospital communities had brought to her shores. The expansion of hospital facilities, sheltered workshops, the constructive loan scheme, the Tuberculosis Rehabilitation Centre, the H o m e for the Aged Tuberculous, are positive achievements. We have even been able, during the past two years gradually to reduce our bed capacity for the tuberculous and at the same time to strengthen further the network of Chest Clinics throughout the country. The beneficial results of these activities, important as they are to the tuberculous themselves, have been matched by the gratifying results of education of the patients' families, the hospital staff and b y the increasing awareness on the part of the community of the importance of the rehabilitation of the tuberculous.
(Concludedfrom page 377) Summary 60 cases of tuberculous meningitis were treated in two series. The first of 35 cases were treated up to the end of I951 and had one year's hospital treatment with Streptomycin and PAS. 28 survived and 7 died. 19 are clinically fit and well, 4 are permanently deaf, 3 wear corrective splints for leg deformities, and 2 are mentally retarded. The second series of 25 cases were treated from I952 onwards and had six months' hospital treatment with Streptomycin, Isoniazid, and PAS. 2o survived and 5 died. O f these 2o survivors, 19 are clinically fit and well and only one shows permanent deafness.
I am indebted to Reckitt & Colman Ltd., Hull, who supplied free the Isoniazid used in the early cases of the second series.
373
Tuberculous Meningitis By S. RUSSELL JAMIESON Castle Hill Hospital, Cottingharn, East Yorkshire This paper is a review of 60 cases of tuberculosis meningitis that have been treated at Castle Hill Hospital, Cottingham, since the introduction of streptomycin in z948. The first series of 35 cases were those admitted up to the end of I95x and they were treated with streptomycin and PAS, and the second series of 25 cases were those admitted after z951 and were treated with streptomycin, PAS, and Isoniazid. On admission all cases were classified as: (I) Early case (E) - fully conscious patient with no focal signs, slight nuchal rigidity but with abnormal cerebrospinal fluid (2). (2) Middle case (M) - fully conscious, but sometimes drowsy and lethargic with nuchal rigiditY and focal signs (I9). (3) Advanced case (A) - unconscious or deeply stuporous patient (39). The diagnosis was confirmed by isolation of the tubercle bacillus from the cerebrospinal fluid in 5 x cases. The 9 from which tubercle bacilli were absent showed other specific signs and symptoms of the disease. The results of treatment were assessed after a survival period of six months from the date of admission and cases were observed up to six years. History of Contact. - A definite history of contact with diagnosed tuberculosis in the home was found in 22 of the 6o cases. Mantoux test was performed in all cases and found to be positive. Radiography. - . Definite abnormalities in the chest x-ray film were seen in 38 of the 6o cases. They comprised (a) a primary complex (usually hilar adenitis with a pulmonary focus) in x6 cases; (b) miliary disease of the lungs in 13 cases; and (c) phthisis in 9 cases. G.S.F. Examination. - The general appearances of the C.S.F., cell count, protein content, chlorides and sugar were estimated monthly along with direct examination for tubercle bacilli and culture on Lowenstein's
medium. If a Mantoux-positive case with no tubercle bacilli on direct examination showed a lymphocytosis with increased protein and lowered sugar and chloride content on two occasions, treatment was begun without further delay. FIRST SERIES Treatment In the first series of 35 cases, all patients were given a six-month course of intramuscular and intrathecal streptomycin combined with oral PAS. The daily dose of intramuscular streptomycin was z gramme and was given to all patients in two twelve-hourly doses of o . 5 gramme. The daily dose of intrathecal streptomycin was zoo rag. for patients of 5 years and over, and 5 ° mg. for those under 5 years. Oral PAS was given in gradually increasing dosage to I8 grammes for patients x2 years and over, 9 grammes for those 5-zI years, and 4-5 grammes for those I - 4 years. PAS was given continuously throughout the patients' stay in hospital in the recommended dosage. O n discharge it was continued as a bacteriostatic agent at a reduced dosage for a further two years. Treatment was given for six days a week, Sunday being a complete rest period. All patients were kept in bed for six months' course of streptomycin treatment. A radiograph of the lungs was taken and full chemical and bacteriological examinations ofthe cerebrospinal fluid were made monthly. Patients were not allowed up until the C.S.F. was normal, and they were kept in hospital for at least one year. Results O f the 35 patients treated, 28 survived and 7 died. O f the 28 survivors, 19 are clinically fit and well, of the remaining 9, 4 are permanently deaf, 3 wear corrective splints for leg deformities and 2 are mentally retarded. Table I shows the details of the 35 cases.
F
F
M
M
F
M
-"8
ix
x4
",
x xo/x',
2
6
48
2o
24/r,0
x6
3
xI 9/x."
x
15 6Do
x3
2
3
4
5
6
7
8
9
xo
IX
Io
x3
x4
x5
x6
z7
F
M
M
M
F
F
M
M
M
M
M
2
x
Sex
Age (years)
Case .No.
7
6
zo
t3
."x
~o
xx
5
x4
x2
z',
---4
28
28
",x
14
x4
History (daj,s)
M
A
M
A
A
M
A
A
A
M
A
M
A
A
A
A
A
Too ill Millary Miliary P.C.
Phthisis o
Uxooo + ,/xooo + x/moo + X/XOOO +
x/moo + Umoo +
+
P.C. o
x/xooo +
P.C.
Miliary
Miliary
o
x/xooo +
x/xooo +
x/xoo
z/moo +
x/moo +
P.C.
+
+
Too ill
x/moo +
x/moo +
+
+
P.C.
//moo +
o
+
+
o
+
o
+
o
o o
+
o
+
+
0
o
o
o
o
0
+
+
+ +
+
o
+
o
Phthisis
//moo +
o
o
Chest x-ray
Direct History exam. of of C.S.F. contact for T.B.
Umooo+ Miliary
Condition on Mantoux admission test
+
+
+
+
q-
+
+
+
+
+
+
0
+
+
+
+
+
Culture of C.S.F. for T.B.
TABLE I. - FIRST SERIES
I6O
5 years
5 years
5 years
5 years
5 years
C.S.F. normal. Full recovery
Recovery. Deafness. C.S.F. normal
Recovery. Mentally retarded. Difficulty in walking. Improving. C.S.F. normal
C.S.F. normal. Full recovery
Recovery. Tuberculous ankle healed
C.S.F. normal. Full recovery
C.S.F. normal. Full recovery
Died
6 years
x26
x55
tuberculous
Recovery. Right hemiplegia, much improved on 58oth day. C.S.F. normal
5 years
x67
slmwed
Relapsed and died 9 months after completion of treatment. P.M. showed tuberculoma of brain
Died
Died. P.M. meningitis
Died
Died
Died
Full recovery. C.S.F. normal. Spu tum negative
Full recovery
Result
5 years
6 days
4~ years
2x days
23 days
x9 days
17 days
x21 days
4 years
5 years
Observation
x6x
z62
x68
x79
6
z(;o
x8
=3
19
x7
I20
14t
x66
Streptomycin treatment (days)
Lrl
t~
r-rrl
C tT~ m 7a (3
tad
Age (years)
2
19 6/to
7
2 .°
x7
5 xi/x.0
23
~ xx/x~
6
18
z4
9/=~
', 6/I-0
2 6/i~
3
x4
8
xo
Case No.
I8
19
~o
~t
.02
.03
.04
.05
.06
27
-08
~9
3°
3t
3°
33
34
35
,/xooo + x/mooo+ =/xoooo+ i/~ooo +
x/xooo +
i1,oooo+ x/1ooo + x/xoooo+ t/x0oo + z/moo +
x/zoooo+ ,/ioooo+ ,/=ooo + xDoooo+ ffIoooo+ x/looo + I/xooo +
M
M
M
A
A
A
A
E
A
M
IVI
M
A
E
M
M
A
7
14
t4
7
x2
8
6
x4
7
14
x4
5
x4
7
ix
x4
xo
Miliary
P.C.
o
P.C.
o
P.C.
P.C.
Miliary
P.C.
P.C.
P.C.
o
o
o
P.C,
o
o
P,C.
Cl,est x-ray
o
+
o
+
o
o
+
o
+
+
o
+
+
o
+
+
o
o
+
o
o
+
o
o
o
o
+
o
+
+
+
+
o
o
o
o
160 x68 t64 x64 x68 x68
o + o + +
4 years
4 years
4 years
4 years
4 years
4 years
Recovery. Deafness. C.S.F. normal
C.S.F. normal. Full recovery
C.S.F. normal. Full recovery
C.S.F. normal. Full recovery
C.S.F. normal. Full recovery
C.S.F. normal. Full recovery
Recovery. Left hemlplegia. Much improved. C.S.F. normal +
6 years
t6o
+
Full recovery'. C.S.F. normal 4 years
Readmitted 6 months after discharge with miliary tuberculosis of lungs. Much improved with 2rid course of dihydrostreptomycin. C.S.F. normal. Deafness
Recovery. Mentally retarded. C.S.F. normal
5 years
C.S.F. normal. Full recovery
6 years
x68
+
4 years
C.S.F. normal. Full recovery
16o
x68
+
4 years
C.S.F. normal. Full recovery
o
i68
+
4 years
C.S.F. normal. Full recovery
C.S.F. normal. Full recovery
Recovery. Deafness. C.S.F. normal
x68
+
4 years
5 years
4 years
x62
+
C.S.F. normal. Full recovery
I7O
x57
+
5 years
C.S.F. normal. Full recovery
+
x6o
+
5 years
Result
x7o
x6o
Observation
0
(days)
+
Streptomycin treatment
C.S.F. for T.B.
of
Culture
P.C. = Primary complex Miliary = Miliary disease of lungs
Direct History exam. of o.f C.S.F. contact for T.B.
M = Middle case A = Advanced ease
,/moo +
Mantoux test
A
IO
E = Early case
M
M
M
M
M
M
F
F
F
F
M
F
F
F
M
M
F
M
Sex
Condition on History (days) admission
tD
rFit
WI
-4 C
t.a"t
ot fD
M M hi F
F
5
~9
2I o9 5 3[I-.q
4 4 5 5
'3 20 2 3]Ia ',
xI ~7 t6
x5 4/I-,,
4
, 6/12
5
6
7 8 9 Io
Ix x2 t3 I.t-
'5
,6 t7 x8
19 2o 2I
22 23
e4
25
4
7
xt 2
x4 x4 ',x
7 6 7
3
5 3° 9 7
to 3° 7 ~o
20
3
5 to 3
Itistory (day~) 8
E Early case
M
F
M F
F F F
F F F
M M M M
F
M
M M F
8 ~x x
..q 3 4
Sex F
Age (years) I7
Case .No. I
+ + + +
x/,ooo +
x/moo +
x/Iooo + x/xooo +
x/xooo + i/Iooo + t/Iooo +
,/moo + I/IOOO+ x/xooo +
x/,ooo +
i/tooo I/*ooo 1]tooo I/tooo
I/xooo + I/,ooo + I/IOOO+ x/iooo +
x/tooo +
,[,ooo +
I/tooo + z/Iooo + l/tooo +
M = Middle case
A
A
A A
A A A
M A A
M
M A A A
A A A A
A
M
A M A
Condition on Alantoux admission test M x/Iooo +
+ o +
o o o o
o
o
+
+
+ + +
+
+
+ + o
+ + + +
+ +
,-[o o
+
q-
+ + o
+
for T.B.
c.s.y.
Culture of
980
9o
9°
~73 21
x4 9x
90 90 90 9° 2I
14 9x
Result
Full recovery Full recovery Full recovery Full recovery Left-sided hemlplegla. N o w full recovery Died. P.M. showed tuberculous meningitis with hydrocephalus Died. Severe bedsores Full recovery Full recovery Full recovery Full recovery Full recovery Full recovery Full recovery Full recovery Full recovery Full recovery Full recovery Full recovery Full recovery Full recovery Deafness, otherwise fit a n d well Died. P.M. showed tuberculous meningitis a n d miliary tuberculosis Died Died. P.M. showed tuberculous meningitis a n d hydrocephalus Miliary = Miliary disease of lungs
598 54 ° 420 2Io 200 200
9° 90 9°
94 93o 900 84 o 776 720 7x6 690 60o
9° 9° 90 9o 90 90 90 9° 9°
x9
x9
1,050 x,o5o 1,020
9° 90
Days of observation I,I IO
Streptomyc~ treatment (days) 9o
P.C. = P r i m a r y complex
+
o
o o o
+ o
o o
+ + +
o o o
o o +
+
+
+
+
o
o
+
o + o
o o o
o
+
:F
o o
for T.B.
contact
o o +
c.s.y,
of
A = A d v a n c e d case
o
Phthisis
Miliary
o
Miliary o Miliary
o O Phthisis
o
Miliary P.C. P.C. Miliary
o o Phthisis lVIiliary
Phthisis
o
o Phthisis Phthisis
Chest x-ray Phthisis
Direct exam. of
tllsto~y
T A B L E II. - SECOND SERIES
,,.o (d-I
-2
rITI
(3
17"1
"-t C
w ",,4
December 1955
T U BERC L E
377
the daily dose and the total dose administered. For example, it has been reported that reTreatment ducing the daily dose of streptomycin from In the second series of 25 cases, patients were 3 grammes to z gramme substantially degiven a three-month course of intra- creased the incidence of vestibular damage muscular and intrathecat streptomycin com- though therapeutic results were in no way bined with oral PAS of the same dosage as impaired. It follows that, though a dose of in the first series. Isoniazid was also given in streptomycin and dihydrostreptomycin toincreasing dosage to zoo mg. t.i.d, for gether will have the same t h e r a p e u t i c patients z2 years and over, and 50 mg. t.i.d. activity as an equivalent dose of either for younger patients. The Isoniazid and antibiotic used alone, if only half as much PAS was given continuously throughout the of each antibiotic is being used there will be patient's stay in hospital in the recommended a reduction in neurotoxic effects because dosage. On discharge both drugs were con- these are different for the two substances. tinued as a bacteriostatic agent, Isoniazid Marked degrees of hearing loss and partial for three months and PAS for a further two deafness form the one serious complication years. Patients were allowed up after comwhich occurs in cases otherwise fit and well pleting their three months' course of strepand the education of the affected patients tomycin and discharged home at the end of would certainly suffer without special educasix months in hospital. tional treatment. Some authorities believe that the deafness Results is due to the tuberculous process and support O f the 25 patients treated, 20 survived and this by the fact that streptomycin has been 5 died. O f these 20 survivors, 19 are clinically extensively used for other forms of tuberfit and well and the remaining one shows culosis and while admitting damage to the permanent deafness. balancing mechanism in the inner ear Table II shows the details of the 2 5 cases. affirm that it is not a cause of deafness when used in the normal dosage. Discussion The occurrence of deafness in cases of During streptomycin - PAS, treatment tuberculous meningitis treated with streprashes, fever, loss of weight, anorexia, tomycin shows considerable variation in vomiting, vertigo, deafness, and albuincidence from place to place and in order minuria occur in varying degrees. With to obtain reliable statistics it would be the exception of deafness, most of these necessary to do objective tests of hearing in symptoms subside when the streptomycin all cases, otherwise cases of high-frequency is stopped. During the past year a comdeafness might easily be missed. bination of streptomycin and dihydroWith Isoniazid, the only serious complicastreptomycin, Dimycin, has been used to tion was the appearance of massive bed sores reduce or eliminate the neurotoxic effects in 2 patients. This was looked upon as a that might develop from using either subnicotinic acid deficiency and all patients stance singly. receiving Isoniazid are also given nicotinic Streptomycin and dihydrostreptomycin acid 5 ° mg. b.i.d. have, for all practical purposes, the same As regards the mental impairment followtherapeutic effect. Both can have a serious effect on the eighth cranial nerve, strep- ing tuberculous meningitis, it is difficult to tomycin affecting primarily vestibular and assess and repeated follow-up examinations dihydrostreptomycin auditory function; ex- are necessary to ascertain whether this is perience has shown that these toxic effects likely to be permanent. (Concluded on page .386) depend to a large degree upon the size of SECOND SERIES
386
T U BERC LE
female patients, who in view of adverse social circumstances cannot look after themselves or cannot be cared for by their relatives. Ever since our unpleasant experience of having to separate a newly arrived elderly immigrant couple, sending the tuberculous husband to a sanatorium and the healthy wife to a home for tile aged, we were convinced of the need to allow couples to live together. The home therefore accepts the healthy marriage partner also. The age of admission has been set at 65 for men and 60 for women, but patients somewhat younger arc also accepted if they are found otherwise suitable. The patients have to be ambulant, not in need of nursing care and able to carry out for themselves the ordinary activities of daily life. Three share a room, married couples have a room to themselves. Apart from recreational activities, nearly all are participating in occupational therapy, make their own beds and take turns in helping in the dining room. The medical team includes a general practitioner, nurses, a social worker, an occupational therapist, a visiting dentist and tuberculosis specialist. Diagnostic facilities allow for x-ray and routine laboratory examinations to be carried out on the spot, while cultures and other special examinations are performed at the laboratory at Beer-Yaacov Hospital. Sick rooms are provided for those suffering from intercurrent illnesses. In case of serious exacerbation of their tuberculous lesion, the patients are admitted to a tuberculosis hospital. Should their social circumstances permit it, the inhabitants might be living in their own homes under Chest Clinic Supervision carrying out the activities of elderly people. The Home for the Aged Tuberculous tries to provide these facilities and at the same time to stimulate the inhabitants to become interested in their own little community, thereby living a fuller life. The H o m e has only been in existence for two and a half years and it is still too early to draw conclusions from our short experience. However, the character of this installation makes its progress a m a t t e r of great interest to us all.
December 195S
Conclusion Faced only five years ago with a task far exceeding existing means; Israel has nevertheless made considerable progress in the rehabilitation and absorption of tuberculous immigrants, whom unselected mass emigration and the wholesale transfer of hospital communities had brought to her shores. The expansion of hospital facilities, sheltered workshops, the constructive loan scheme, the Tuberculosis Rehabilitation Centre, the H o m e for the Aged Tuberculous, are positive achievements. We have even been able, during the past two years gradually to reduce our bed capacity for the tuberculous and at the same time to strengthen further the network of Chest Clinics throughout the country. The beneficial results of these activities, important as they are to the tuberculous themselves, have been matched by the gratifying results of education of the patients' families, the hospital staff and b y the increasing awareness on the part of the community of the importance of the rehabilitation of the tuberculous.
(Concludedfrom page 377) Summary 60 cases of tuberculous meningitis were treated in two series. The first of 35 cases were treated up to the end of I951 and had one year's hospital treatment with Streptomycin and PAS. 28 survived and 7 died. 19 are clinically fit and well, 4 are permanently deaf, 3 wear corrective splints for leg deformities, and 2 are mentally retarded. The second series of 25 cases were treated from I952 onwards and had six months' hospital treatment with Streptomycin, Isoniazid, and PAS. 2o survived and 5 died. O f these 2o survivors, 19 are clinically fit and well and only one shows permanent deafness.
I am indebted to Reckitt & Colman Ltd., Hull, who supplied free the Isoniazid used in the early cases of the second series.