The diagnostic pathway in amyotrophic lateral
sclerosis
Yasuo Iwasaki
1, Ken Ikeda1,2 and Masao Kinoshita1
ALS and other motor neuron disorders 2001 2, 123–126 © 2001 ALS and other motor neuron disorders. All rights reserved. ISSN 1466-0822
123
Introduction
Amyotrophic lateral sclerosis (ALS) is a relentlessly devastating
disease of the central nervous system in which
motor neurons die over a relatively short time period, the
victim becomes progressively paralysed, and death occurs
as a consequence of respiratory insuf.ciency resulting
from that paralysis. Accurate diagnosis of a patient presenting
with suspected ALS is important, but early diagnosis of
ALS is often dif.cult. Confusing ALS with another, often
more benign, motor neuron disease or with a non-motorneuron
disease may result in inaccurate prognosis and no
proper management program.
It is important to investigate how patients with ALS are
referred to a neurologist, and what is the time lapse
between the appearance of the .rst symptoms of ALS and
con.rmation of the diagnosis. There have been several
reports from different countries concerning the time taken
to diagnose patients with ALS. Belsh and Schiffman
1
reported the medical records of 33 patients with de.nite
diagnosis of ALS in the US, and showed that the mean
time to diagnosis was 11.2 months. In a European group
of 91 patients with ALS, the mean time between the .rst
1
Toho University Ohashi Hospital, Tokyo
2
Department of Neurology, PL Tokyo Health Care
Center, Tokyo
Correspondence:
Yasuo Iwasaki, MD
The Fourth Department of Internal Medicine
Toho University Ohashi Hospital
2-17-6, Ohashi, Meguro-ku, Tokyo, 153-8515
Japan
Tel: (
1 81) 3-3468-1251
Fax: (
1 81) 3-3468-5082
Received 2 January 2001
Revised 3 August 2001
Accepted 15 August 2001
INTRODUCTION: We present the .ndings
of a survey of the diagnostic pathways
and treatment of 50 patients with amyotrophic
lateral sclerosis (ALS).
RESULTS: The mean time between .rst
symptoms and .rst consultation with a
physician was 5.7 months; mean time
between .rst symptoms and .rst consultation
with a neurologist was 9.7 months;
mean time from symptom onset to con.rmation
of diagnosis was 11.6 months.
Patients with bulbar onset appeared to
be diagnosed earlier than those with limb
onset, but the difference was not statistically
signi.cant. The .rst physician seen
was an orthopedist in 30%, a general
practitioner (GP) in 28%, and a neurologist
in 28% of cases. The mean diagnostic
intervals were 9.4 months when
the neurologist was the .rst physician
seen, and 9.8 months when the neurologist
saw a patient referred from a
GP. Otherwise, when a neurologist saw
patients referred from an orthopedist,
the mean diagnostic interval was 14.9
months. Differences between the values
of mean diagnostic interval were not statistically
signi.cant. EMG and MRI were
performed in all patients, cerebrospinal
uid examination and muscle biopsy in
most. Treatment was by vitamins in 38%
of cases, thyrotropin-releasing hormone
in 24%, physical therapy in 22%, and
anticholinesterase agent in 12%.
CONCLUSION: The number of patients in
our study is limited, and a further
prospective nation-wide survey is necessary.
(ALS 2001; 2: 123–126)
Keywords:
amyotrophic lateral sclerosis – neurologist – general practitioner –
interval – early diagnosis
symptom and diagnosis con.rmation was 12.2 months.
2
In a South American group of 60 patients, in an international
survey, the mean time from symptom onset to
con.rmation of diagnosis was found to be 16.6 months.
3
Househam and Swash found that in England and Wales,
the mean time from onset to diagnosis of ALS was 16.2
months.
4 Other epidemiological studies have reported
median times needed to establish diagnosis ranging from
1 to 2 years.
5,6
At present, the management of ALS varies considerably
from country to country, depending on national referral
systems and healthcare organization, among other factors.
This article retrospectively reviews our experience over a
6-year period with a group of patients with ALS in our
department.
Methods
We reviewed the hospital records of all our cases of
ALS. The diagnosis was based on the World Federation of
Neurology (WFN) criteria for de.nite and probable ALS.
7
The objective of this study was to identify the pathway
Amyotroph Lateral Scler Downloaded from informahealthcare.com by University of Connecticut on 05/12/10
For personal use only.
in 28% of all cases, although 30% of cases .rst consulted
an orthopedic specialist. A neurologist was the .rst physician
to see 28% of cases, and the second in 52% of cases;
so 80% of cases saw a neurologist either .rst or second. An
otolarynologist saw two cases with ALS in the .rst
instance; these two cases were bulbar onset patients. Of 14
patients who presented directly to a neurologist with
initial symptoms, the mean time needed for the neurologist
to diagnose ALS was 9.4 months. Among these 14
patients with ALS, 13 cases were de.nite and one was
probable; 11 patients had bulbar onset, and three patients
had limb onset. Of 14 patients who visited a GP .rst,
eleven of whom were referred to a neurologist, the mean
interval between onset and con.rmation of diagnosis of
ALS was 9.8 months; of these cases, nine were de.nite and
.ve probable, and nine had limb onset and .ve had
bulbar onset. An orthopedist saw 15 cases of ALS at .rst
visit, and four of these cases were referred to another
orthopedist. Another orthopedist also saw one case
referred by a GP. Where a neurologist saw ALS cases who
were referred by an orthopedist, the mean time taken to
followed by ALS patients from the .rst symptoms to .nal
diagnosis, to determine which physicians were seen and
when, patients’ attitudes and reaction, and what was the
role of the neurologist along the diagnostic pathway.
Further objectives were to quantify the time taken to reach
diagnosis and the relative contributions of the different
processes to the overall time to diagnosis, as well as to
determine what types of examinations and tests were used
for diagnosis and what types of treatments were performed.
Results were strati.ed according to sex, age, and
initial symptoms (bulbar versus limb onset).
Results
Overall demography
A total number of 50 patients were recruited, 29 (58%)
men and 21 (42%) women. Initial symptoms appeared at
a bulbar site in 25 (50%) and limb site in 25 (50%) cases.
The age of onset varied from 37 to 79 years, and peaked at
60–69 years (38%), and 50–59 years (30%), for men and
women respectively. Only 2% of patients were younger
than 40 years, and only 4% older than 79 years. There
were 37 de.nite and 13 probable cases, according to the
WFN criteria for ALS.
7 The mean age at onset of symptoms
was 61 years (Figure 1).
Time to con.rmation of diagnosis
The time elapsing between the .rst symptoms and .rst
consultation varied from 1 to 28 months, with a mean of
5.7 months. The time elapsing between the .rst symptoms
and .rst consultation with a neurologist varied from 1 to
28 months, with a mean of 9.7 months. The mean time
elapsing between .rst symptoms and con.rmation of
diagnosis was 11.6 months. Patients with limb onset
apparently .rst saw a physician earlier than did those with
bulbar onset; but patients with bulbar onset appeared to
be diagnosed earlier than those with limb onset. There
were no signi.cant differences for the time to con.rmation
of diagnosis between bulbar and limb onset ALS patients
(Figure 2).
The .rst physician seen was a general practitioner (GP)
124
Y Iwasaki, K Ikeda and M Kinoshita
Original Research
(%)
0
,
40
50
40
30
20
10
Age (
n5 50)
Sex (
n5 50)
Female
42%
Male
58%
Initial symptoms (
n5 50)
Limb
onset
50%
Bulbar
onset
50%
40–49 50–59
. 79
Years
60–69 70–79
38%
30%
14%
2%
12%
4%
Figure 1
Demographic data.
First symptoms and
first consultation
First symptoms and
first consultation
with neurologist
First symptoms and
diagnosis confirmation
5 6 7 8 9 10 11 12 13 14
5.1
6.4
5.7
9.7
10.3
8.6
11.6
10.6
12.9
total bulbar onset limb onset
Time elapsed between, in months (
n5 50)
Figure 2
Time taken to reach con.rmation of diagnosis.
Amyotroph Lateral Scler Downloaded from informahealthcare.com by University of Connecticut on 05/12/10
For personal use only.
Diagnostic pathway in ALS
125
Original Research
Diagnosis
between
(mean)
1–33mos
(9.4)
6–28mos
(15.6)
6–24mos
(9.8)
2–48mos
(14.9)
NS: neurosurgeon
GP: general practitioner
ORTH: orthopedist
ENT: otolaryngologist
NEUROLOGIST
14 7 11 16 2
NS GP ORTH ENT
1 4 2
5 14 15 2
50 patients
2 1
Figure 3
Pathway from the appearance of the .rst symptoms
to con.rmation of the diagnosis.
EMG 50 (100%)
MRI 50 (100%)
CSF 45 (90%)
Muscle biopsy 37 (74%)
Table 1
Examinations and tests used for diagnosis (n
5 50).
reach diagnosis was 14.9 months. Of these patients 13
were limb onset and two were bulbar onset (Figure 3).
Tests and examinations
The tests and examinations used to con.rm the correct
diagnosis of ALS are summarized in Table 1. EMG, which
is essential for con.rmation of the diagnosis, was
employed in all the cases. Brain and cervical MRI, which
aids in the exclusion of other disorders, was also used in
all the cases. The same is true of spinal punctures, performed
in 90% of cases. Muscle biopsies were also
common in our department (74% of cases). Muscle biopsy
was usually undertaken as the .nal diagnostic procedure,
and muscle biopsy does not seem to hasten the diagnosis.
Measurement of motor-evoked potentials was much less
often performed in our department (Table 1).
Treatment
The initiation of treatment was also a consequence of
diagnosis, and the type of treatment varied (Table 2). Vitamins
were widely prescribed in 38% of cases. Thyrotropinreleasing
hormone was used in 24% of cases. Physical
therapy was performed in 22% of cases. Anticholinesterase
was given in 12% of cases. No cases had anti-inammatory
drugs. No patient was given riluzole, because our hospital
committee had not approved the use of riluzole in our
department during this period. Riluzole is however now
available in our hospital.
Discussion
The diagnosis of ALS is achieved by clinical examination
and a series of investigations designed to exclude other
clinical syndromes. ALS may be mimicked by cervical
myelopathy secondary to spondylosis or other cervical
cord diseases, multiple sclerosis, lacunar stroke, certain
multifocal motor neuropathies and foramen magnum
lesions. Belsh and Schiffman
1 reported that 14 out of 33
patients (43%) with ALS were initially misdiagnosed. They
suggested that early diagnosis of ALS may help to prevent
medical mismanagement and may bene.t patients both
medically and psychologically; early diagnosis is increasingly
important.
Several epidemiological studies have reported diagnostic
intervals ranging from one to two years.
1–5 Referral
Vitamins 19 (38%)
TRH 12 (24%)
Physical therapy 11 (22%)
Anticholinesterase 6 (12%)
Table 2
Treatment (n
5 50)
Amyotroph Lateral Scler Downloaded from informahealthcare.com by University of Connecticut on 05/12/10
For personal use only.
systems, healthcare systems, diagnostic procedures and the
therapy and management of ALS patients vary considerably
from country to country. A European study found
that diagnosis of ALS was always made by a neurologist;
8
and in all the cases in our study, neurologists in our
department have made the diagnosis of ALS. Our study
found that the mean diagnostic interval was 9.4 months
when the neurologist was the .rst physician seen, and 9.8
months when a neurologist saw patients who were referred
from a GP. When a neurologist saw cases referred from an
orthopedist, the mean diagnostic interval was 14.9
months. There were no statistically signi.cant differences
in mean diagnostic interval between cases .rst seen by a
neurologist and cases referred to a neurologist by a GP or
orthopedist.
Healthcare systems differ from country to country. In
Japan, few neurologists practise privately or as GPs; most
are af.liated to university or national hospitals or
community-based hospitals. Most GPs in Japan are general
internists and they are not familiar with ALS patients; most
GPs will have only one or two patients with ALS under
their care during their working life.
4 If patients visit a university
hospital .rst, they have to pay more than if they are
seen by a GP .rst. One third of the patients in our survey
visited a neurologist .rst, one third a GP, and one third an
orthopedist. This indicates that patients know that neurologists
are mostly working in university-based hospitals;
but these hospitals are very busy and patients have to
spend half a day to see the neurologist; seeing a GP is
much more convenient and saves time.
There are several reasons for the average time lapse of
9.4 months between neurologist consultation and diagnosis.
Some patients don’t visit regularly. Some came to our
department in the .rst instance, then changed to another
hospital to get more information or because they thought
it a more prestigious institution, but .nally came back to
our department again. Some patients don’t want to visit
our department regularly because they don’t want to know
their correct diagnosis as ALS is a tragic disease. Despite
the regular visits the patients’ conditions deteriorate, and
they may temporarily give up coming to us.
It is interesting that of the 14 patients who initially saw
their GP, 11 were diagnosed within 9.8 months. These
patients were referred by their GP, who said they should
visit our department regularly, so diagnostic procedures
seem to go smoothly in these cases. GPs in Japan are
extremely unfamiliar with neurological cases. A typical reference
might run: ‘Is this a neurological case? Please make
correct diagnosis’ and there is no reference to any suspicion
of ALS. In a few instances, there appeared to be a
reluctance on the part of the GP to refer the patients to a
specialist, as Househam and Swash
4 pointed out. But this
is not reected in our results.
When patients were referred from an orthopedist, the
diagnostic interval was much longer: 13 out of these 16
cases were limb-onset ALS patients, with little involvement
of bulbar sign; four of these patients were actually referred
to another orthopedist.
In practice, when physicians see a patient with fasciculations,
ALS is the .rst condition that comes to their mind.
Forty-six out of 50 patients had fasciculation in our series.
A correct and early diagnosis of ALS may help the physician
to spare the patient from prolonged hospitalization
and expense, and sometimes from painful diagnostic procedures
and treatments.
The number of patients in our survey is relatively small,
so that a future nation-wide survey is needed.
References
1. Belsh JM, Schiffman PL. Misdiagnosis in patients with amyotrophic
lateral sclerosis. Arch Intern Med 1990; 150:
2301–2305.
2. Dengler R. Current treatment pathways in ALS: a European
perspective. Neurology 1999; 53 (Suppl 5): S4–S10.
3. Dubrovsky AL, Sica REP. Current treatment pathways in ALS:
a South American perspective. Neurology 1999; 53 (Suppl
5): S11–S16.
4. Househam E, Swash M. Diagnostic delay in amyotrophic
lateral sclerosis: what scope for improvement? J Neurol Sci
2000; 180: 76–81.
5. Norris F, Shepherd R, Denys E, et al. Onset, natural history
and outcome in idiopathic adult motor neuron disease. J
Neurol Sci 1993; 118: 48–55.
6. Chio A. ISIS survey: an international study on the diagnostic
process and its implications in amyotrophic lateral sclerosis.
J Neurol 1999; 246 (Suppl 3): 1–5.
7. World Federation of Neurology Research Group on Neuromuscular
Disease. El Escorial World Federation of Neurology
criteria for the diagnosis of amyotrophic lateral sclerosis. J
Neurol Sci 1994; 124 (Suppl): 96–107.
8. Pongratz D. The diagnostic process in ALS. J Neurol Sci
1999; 165: S10–S13.
126
Y Iwasaki, K Ikeda and M Kinoshita
Original Research
Amyotroph Lateral Scler Downloaded from informahealthcare.com by University of Connecticut on 05/12/10
For personal
No comments:
Post a Comment