Results of a questionnaire in 100 ALS patients and 100 control cases

W . A . de n H a r t o g Jage r* , P .W. H a n l o * *, B . J . J . Ans ink* * *, and M . B . M . V e r m e u l e n * * * *

A series of questionnaires on ALS and its prob- lems has already been published in the literature. This questionnaire is the first in the Netherlands.

Material and methods

The questionnaire was sent to nearly all Dutch neurologists and some other physicians. 54 questions were subdivided in 8 subgroups: I. heredity, II. nutrition, III. medicines used, IV. intoxications, V. previous infectious diseases, VI. vaccinations or serum injections, VII. miscellaneous and VIII. special remarks (see appendix).

106 answers returned. The first 100 were used. An attempt was made to prepare a sex-and age- matched control series. Therefore, the same questionnaire was sent to all neurologists and other physicians who had sent in the question- naire on one (or m o r e ) A L S patients. They were asked to use a control patient of the same sex and age (+ or - 5 years) not suffering from ALS but with complaints of headache, dizziness or with a disc hernia. We received only 25 ans- wers.

The remaining 75 questionnaires were filled in by two of the authors (B.J . J .A. and M.B.M.V. ) who used data from there outpatient material. The ALS- and control group are therefore sex- and age-matched but geographically different. ALS is well known for its homogeneous inci-

Summary

A questionnaire with 54 relevant questions was studied in 100 ALS patients and 100 age and sex matched control cases. The findings were discussed in relation to 7 questionnaires in the literature. No differences were found between ALS patients and controls. Especially the in- crease of frequency of gastrointestinal opera- tions, previous poliomyelitis, toxic metal ex- posure frequency, antecedent fractures and excess milk drinking as described in the litera- ture were not confirmed.

Key words: Amyotrophic lateral sclerosis, questionnaire, etiology.

dence all over the world (except for G U A M and the Kii Peninsula in the Pacific).

The headings of heredity (I) and medicaments (III) were omitted in the questionnaire of the control cases. The total number was also 100.

The significance of the findings calculated with the Z-score: 0,1 (10%), 0,05 (5%) or 0,01 (1%). 0,01 signifies that the two series are different with a 1% chance that the conclusion is wrong. 0,05 signifies that the two series are different with a 5% chance that the conclusion is wrong. 0,1 (10%) is not acceptable as measure of difference. The numbers 'unknown' (?) were added in the same proportion (50%) to controls and patients.

* Department o f Experimental Neurology, Amsterdam Medical Centre, Amsterdam, * * Dutch A.L.S. Society, Bergen N.H., * * * St. Lucas Hospital, Amsterdam, * * * * Elisabeth Hospital, Amersfoort

Address for correspondence and reprint requests: W.A. den Hartog Jager, Department o f Experimental Neurology 61-140, Amsterdam Medical Centre, Meibergdreef 9, 1105 A Z Amsterdam, the Netherlands

Accepted 12.12.86

Clin Neurol Neurosurg 1987. Vol. 89-1

37

Results (see appendix) Discussion

We will discuss the most important findings in relation to the questionnaires in the literature.

We will discuss: I Heredity. The number of hereditary or

familial cases was small (2%). There were no twins who were both affected.

II Nutrition. The number of patients with a previous history of peptic ulcer or ulcer complaints was 20 in the ALS series and 15 in the control group. The number of stomach or intestinal operation was higher in the control group (28) than in the ALS group (19)..

III Drug exposure in the ALS group was high

(88). Beneficial or negative effects were reported by 13 resp. 12 ALS patients.

IV The number of patients exposed to lead was 10 in control cases and 7 in patients. The exposure to other metals (toxic or not) was relatively low and not significantly dif- ferent in the ALS group and the control group.

V Infectious diseases in the previous history was for poliomyelitis controls 2, and ALS patients 1 . Except for herpes zoster the numbers for the controls were always higher than for the ALS patients.

VI Vaccinations or serum injections were higher for the control cases than for the ALS patients.

VII Miscellaneous. The number of fractures in the previous history was 26 in the controls and 24 in the patients. Consumption of milk was slightly higher in ALS patients (67) than in controls (62). The difference is not significant. All the

other questions were equal or higher in the control group than in the group of ALS patients.

VIII A 0,01 result in the Z-score was found in poliomyelitis vaccination (higher number in controls than in ALS patients). A 0,05 result in the Z-score was found in tetanus vaccination, hypertension and herpes simplex infection (higher number in controls than in ALS patients).

It is unavoidable that part of the questions is not answered. However , there is no reason to believe that there should be a difference between the two groups in the degree of forgetfulness, as the in- tellectual capacity of ALS patients is normal.

Ask-Upmark j observed ALS in 5 persons after gastric resection. Stiel 2, however, found not a single case of gastrectomy in a group of 125 pa- tients and only 10 patients were recorded as hav- ing suffered from peptic ulceration. In our material 19 ALS patients underwent a stomach or intestine operation but this was registered in 28 control cases. Therefore this questionnaire found no arguments for an absolute or condi- t ioned nutritional deficiency secondary to a gastricintestinal malfunction.

Felmus e t a l 3 found in 25 ALS patients more ex- posure to lead and mercury and consumption of larger quantities of milk in ALS patients than in control cases. This is not confirmed by our study.

Kondo 4 found no predisposition for ALS after gastrectomy. He examined an exceptionally large series of ALS patients (458 men, 254 women) and control cases (216 men and 421 women).

Kurtzke and Beebe 5 found an excess in the number of truck drivers in 36 ALS patients, all World War II veterans. They also found signifi- cantly more histories of trauma or surgical opera- tions and a significant excess of fractures of the limbs. We could not confirm this. Kondo and Tsubaki 6 found in the same material of Kondo 4 that mechanical injuries were 2-3 times more fre- quent in both sexes in motor neuron disease. No association was found with 23 other risk factors. Pierce-Ruhland and Patten 7 found greater ex- posure to lead and mercury and a larger con- sumption of milk in 80 ALS patients than in sex- and age matched controls. The interviews were done by telephone, which is not a very good approach to the problem and the patients. This was not found in our series of patients.

Gawel, Zaiwalla and Clifford Rose 8, found an antecedent history of back injuries more often in ALS patients, but no increase of fractures, malig- nancy or previous poliomyelitis (studied were 63 motor neuron disease patients and 61 control cases). Back injuries were not studied separately

38

by us but otherwise we confirmed the findings of Gawel et al.

The absence of a higher incidence of fractures in the history of ALS patients is an argument against the hypothesis that osteoporosis and a Ca metabolism disturbance are of causal signifi- cance in ALS patients.

Roelofs-Iverson et al 9 reported on a question- naire with 181 questions with 103 replies and 164 controls.

In all but a few items, the responses of the ALS cases and controls did not differ significantly. In heavy metal exposure (metals not specified) a significant level of shared exposure was found. However the exposure was in 17 of 45 male ALS patients (38%) and only in two cases of 47 women with ALS (4.2%). It is not very probable that metal intoxication could be an etiological factor in ALS in men and not in women.

Comment

A questionnaire is a too crude technique for searching for etiological factors in A.L.S.

Acknowledgements

We thank our colleagues who co-operated in sending back the questionnaires as well as W. Bles Ph.D. for calculating the Z-score, the ALS Society of the Netherlands and Miss E.M. Goossens for administrative and secretarial help.

References

1 ASK-UPMARK E. Amyotrophic lateral sclerosis observed in 5 persons after gastric resection. Gastroenterology 1950; 15:257-9.

2 STIEL JN. The incidence of gastrectomy and gastric secretion in motor neuron disease. Aust Ann Med I967; 16:176-7.

3 FELMUS MT, PATI~EN BM, SWANKE L. Antecedent events in amyotrophic lateral sclerosis. Neurology 1976; 26:167- 72. KONDO K, Does gastrectomy predispose to amyotrophic lateral sclerosis? Arch Neuro11979; 36:586-7.

5 KURTZKE JF, BEEBE GW. Epidemiology of amyotrophic lateral sclerosis: 1. A case-controtcomparison based on ALS deaths. Neurology 1980; 30:453-62.

6 KONDO K, TSUBAKI T. Case-control studies of m o t o r

neuron disease. Association with mechanical injuries. Arch Neurol 1981; 38:220-6.

7 PIERCE-RUHLAND R, PATTEN BM. Repeat study of a n t e c e -

d e n t events in motor neuron disease. Ann Clin Res 1981; 13:102-7.

8 GAWEL M, ZAIWALLA Z, CLIFFORD ROSE F. Antecedent events in motor neuron disease. J Neurol Neurosurg Psychiatry 1983; 46:1041-3.

9 ROELOFS-IVERSON RA, MULDER DW, ELVEBACK LR, KUR-

LAND LT, MOLGAARD CA, Neurology 1984; 3 4 : 3 9 3 - 5 .

39

Append~

Amyotrophic lateral sclerosis questionnaire 1. Name physician 2. Address physician 3. Telephone number 4. Name patient (initials only) 5. Age patient 6. Age a t start of the disease 7. Sex of the patient 8. Latest profession of the patient 9. Earlier professions of the patient

10. City or town of the patient

I. Heredity (or familial occurrence) 1. Does the disease occur in the

family of the patient: grand- parents, parents, children, brothers, sisters, uncles, aunts, cousins, �9 nephews or nieces?

2. Is the patient one of twins? 3. If so, are both suffering from ALS

or only one? 4. Is there more than one ALS patient

in one household'? II. Nutrition

Did the patient have a special diet before the start of the disease? If so, what kind of diet. Was the patient suffering from 1. chronic diarrhea 2. malabsorption syndrome 3. sprue 4. peptic ulcer 5. Crohn's disease 6. ulcerative colitis 7. did the patient have an operation

of stomach or intestine 8. other stomach or intestine disease

III. Medication 1. Did the patient have any medicin

with beneficial results. Which? 2. Did the patient have any medicin

with detrimental results. Which? IV. Intoxications

Was the patient exposed to metals or metal compounds, for instance

1. lead 2. mercury 3. cadmium 4. aluminium 5. selenium 6. manganese 7. copper 8. silver 9. other metals or metal compounds

10. organic substances in profession Which?

If confirmative, please report when the intoxication took place (profession, factory, hobby and so on)

40

1. 2. 3. 4. 5. 6. 7. 8. 9.

10.

1,

2. 3.

4.

1. 2. 3. 4. 5. 6. 7.

8.

1.

2.

1. 2. 3. 4. 5. 6. 7. 8. 9.

10.

C P C P 26 26 ~ 74 74

C P C P C P

V. Previous infectious diseases 1. poliomyelitis 2. herpes simplex (mouth, genitals) 3. herpes zoster 4. parotitis 5. hepatitis 6, infectious mononucleosis 7. morbilli 8. rubella 9. varicella

10 E . C . H . O . - Coxsackie virus 11. diphteria 12. scarlet fever 13. whooping-cough VI.

Previous vaccinations or serum injections 1. poliomyelitis 2. morbilli 3. rubella 4. te tanus 5. diphteria 6. whooping-cough 7. hepatitis

VII. Miscellaneous 1. Does the patient have animals at

his/her home? If so, which animal? 2. Previous fractures or fractures

during the disease One or more? Which localisation?

3. Milk consumption? 4. Smoking habits? 5. Consume of alcohol? 6. Hypertension? Which degree? 7. Diabetes mellitus? 8. Operat ions? Which one?

Relation with start of the disease 9. Serious accidents?

Relation with start of the disease 10. Has the patient been in a Ge rman or

Japanese prisoners camp? Which one?

NO

1. 93 88 2. 70 72 3. 87 77 4. 52 50 5. 88 82 6. 93 84 7. 12 15 8. 51 42 9. 32 27

10. 81 45 11. 85 75 12. 86 71 13. 81 69

1. 63 69 2. 88 77 3. 88 75 4. 42 43 5. 62 56 6. 67 59 7. 89 75

1. 44 45

2. 72 74

3. 31 16 4. 43 48 5. 50 46 6. 70 83 7. 93 92 8. 21 39

9. 88 87

10, 87 92

05 11 05 16 06 12 08 24 05 11 05 15 16 27 25 39 23 39 17 54 06 18 07 26 08 23

14 25 09 23 09 24 08 28 13 30 11 30 08 24

06 14

02 02

07 17 05 03 04 04 01 01 00 01 02 01

00 02

O1 02

YES

02 01 25 12 07 11 40 26 07 07 02 O1 72 58 24 19 45 34 02 01 O9 O7 07 03 11 08

23 06 03 00 03 01 50 29 25 14 22 11 03 01

50 41

26 24

62 67 52 49 46 50 29 16 07 07 77 60

05 12 11

01 12 06

C = control case P = ALS patient ? = answer not known by control case or ALS patient

41