Multiple

Sclerosis
http://msj.sagepub.com/

Sensory symptoms of multiple sclerosis: a hidden reservoir of morbidity

Alex D Rae-Grant, Nancy J Eckert, Sharon Bartz and James F Reed
Mult Scler 1999 5: 179
DOI: 10.1177/135245859900500307
The online version of this article can be found at:
http://msj.sagepub.com/content/5/3/179

Published by:
http://www.sagepublications.com

On behalf of:
European Committee for Treatment and Research in Multiple Sclerosis

Americas Committee for Treatment and Research in Multiple Sclerosis

Pan-Asian Committee for Treatment and Research in Multiple Sclerosis

Latin American Committee on Treatment and Research of Multiple Sclerosis

Additional services and information for Multiple Sclerosis can be found at:
Email Alerts: http://msj.sagepub.com/cgi/alerts
Subscriptions: http://msj.sagepub.com/subscriptions
Reprints: http://www.sagepub.com/journalsReprints.nav
Permissions: http://www.sagepub.com/journalsPermissions.nav
Downloaded from msj.sagepub.com at National Dong Hwa University on April 6, 2014

Citations: http://msj.sagepub.com/content/5/3/179.refs.html

>> Version of Record - Jun 1, 1999

What is This?

Downloaded from msj.sagepub.com at National Dong Hwa University on April 6, 2014

Multiple Sclerosis (1999) 5, 179 183

1999 Stockton Press All rights reserved 1352 4585/99 $12.00
http://www.stockton-press.co.uk/ms

Sensory symptoms of multiple sclerosis: a hidden reservoir of morbidity

Alex D Rae-Grant1, Nancy J Eckert1, Sharon Bartz1 and James F Reed*,1
1

Division of neurology and research department, Lehigh Valley Hospital, Allentown, Pennsylvania, USA

Objective: To assess the frequency and quality of sensory symptoms in a population of patients with Multiple Sclerosis (MS) and compare them
with controls. Design: Survey to target population and control group evaluating demographic data, data on disease course, presence of various
symptoms of MS. Setting: Neurological practices afliated with a tertiary community hospital. Participants: 224 patients with MS, 93 controls
of similar age and sex. Results: Sensory symptoms were more common in MS patients than in controls, and differed in severity and quality. Fifty
per cent described brief (seconds to hours) episodes of neurological dysfunction, signicantly more often than in controls (P=0.001). Pain was
present at some time in similar percentages in patients and controls, but active pain problems were present more often in MS patients (P=0.001).
The qualitative description of pain in MS patients was more often neuropathic, with burning, itching, electric and formicatory pain, as opposed to
throbbing, sharp or muscular pain. Pain was localized to arms, legs, trunk, hands, feet and face more often in the MS group. Lhermitte's
phenomenon was present in two-thirds of patients at some time in their disease course. Twenty per cent of the patients identied themselves as
having respiratory problems (Controls 7.5%, P=0.005). Fatigue limited activity in 78% of patients, but only in 17% of controls (P=0.001).
Dizziness, memory dysfunction, and restless legs symptoms were all more frequent in patients. The self-rated `worst' symptoms of MS was pain in
12%, fatigue in 17% and dizziness in 5%, a total of 34% of `worst' symptoms. Sensory symptoms were present in patients with early disease and
without disability as often as in disabled patients and in those with longer disease duration. There was however a strong correlation between the
total number of sensory symptoms reported and the presence of disability in the MS patients. Conclusions: Sensory symptoms are common in
MS patients. Pain syndromes, transient neurologic events, Lhermitte's phenomenon, fatigue, respiratory symptoms and vertigo were present
signicantly more frequently in patients with MS than in a control population and contributed to subjective morbidity. Future clinical trials assessing
therapy in MS might include sensory symptoms as secondary endpoints to capture this `hidden reservoir' of disease morbidity.
Keywords: multiple sclerosis, pain, headache, fatigue, respiration, sensation, Lhermitte's, vertigo

Introduction
Standard measures of Multiple Sclerosis (MS) are
weighted heavily toward items of objective function
such as weakness, reex change, cranial nerve
function, ataxia, visual acuity, and optic atrophy.1,2 In
clinical practice a variety of sensory symptoms may be
prominent in MS, and these symptoms have not been
assessed quantitatively in the medical literature. We
undertook a community-based survey to assess the
frequency of these symptoms in a group of multiple
sclerosis patients, and compared them with an age and
sex matched `healthy' population.

Materials and methods

We developed a data base of 425 patients with
multiple sclerosis in the Lehigh Valley, identied
through the practices of local neurologists. Patients
known to be deceased or unable to complete of
questionnaire were excluded, leaving 387 MS patients
eligible for the survey.
The control group consisted of employees of local
medical ofces and a life insurance company. The
control group was asked to complete the same
questionnaire as the MS group. These two types of
controls were chosen because they consisted primarily
of females of working age, similar to the anticipated

*Correspondence: JF Reed
Received 6 November 1998; revised 10 February 1999;
accepted 12 February 1999

makeup of the patient group. Questionnaires were

handed out and picked up at these ofces.
Condentiality of responses was respected by
omitting names from the returned surveys. The survey
consisted of a series of questions, including demographic data (age, sex, disease duration, disability,
presence of attacks, disease pattern, etc.) Questions
designed to classify the multiple sclerosis were
included, using a recent classication scheme.3 Questions about sensation, gait, strength, functional ability,
memory, seizures, spasticity, fatigue, headaches, pain,
transient neurological events, respiratory function,
urological function, menstrual cycle, heat and coldexacerbation, and Lhermitte's phenomenon were
included. Specic injury was directed to sensory
symptoms including transient neurological events,
headache, pain, respiratory symptoms, fatigue, vertigo,
and Lhermitte's phenomenon.
These data were assessed using Pearson's R likelihood ratio, Mantal-Haenszel test for linear association, Spearman correlation, Student's t-test, and
logistical regression analysis.

Results
Of 387 patients the questionnaire was sent to, there
were 224 responders (58% return rate). The average
age for the responders was 43+9 years (range 24 74).
There were 161 females (72%), and 63 males (28%).
The duration of multiple sclerosis varied from one to
greater then 30 years. Two per cent of the patients had
less than 1 year duration of the disease, 13% 1 3
years, 20% had 4 6 years, 24% 7 10 years, 30% 11

Downloaded from msj.sagepub.com at National Dong Hwa University on April 6, 2014

Sensory symptoms of multiple sclerosis

AD Rae-Grant et al

180

20 years, 9% 21 30 years, and 2% over 30 years

duration (Figure 1).
There were 93 responders from 100 surveys
distributed to controls. There were 76 females and 15
males, with two not responding to this survey item.
The average age was 41+11 years.
The self-classication of MS type was benign (15%),
relapsing returning to normal (31%), relapsing with
accrued decits (25%), progressive relapsing (8%),
secondary progressive (11%) and primary progressive
(8%) (Figure 2). 134 patients described themselves as
not disabled, and 88 patients described themselves as
being disabled. Two patients did not reply to this
question. None of the control group dened themselves as being disabled. Two-thirds of the patients
described themselves as having `attacks' of MS.
Transient neurological events
For the purposes of the study, transient neurological
events were dened as events lasting seconds to
minutes of neurological symptoms not compatible
with an acute exacerbation of multiple sclerosis. 106/
213 patients (50%) stated that they had had such
events. The symptomatology of these events varied
(Table 1). Altered sensation, movement, difculty
speaking, pain, and visual symptoms were characteristic. A variety of descriptions of these transient events
were used by the patients (Table 2). Patients were
asked the time course for the transient neurological
events from rst to last event. The time course of the
events varied from days in 35% of patients, weeks in
17%, months in 10%, and years in 39% of patients.
There was no signicant correlation between the

presence of transient neurological events and disease

duration (Pearson's R=0.05136, signicance 0.47), and
no correlation with the presence of disability (Pearson's R=0.060, signicance P=0.402). The control
group reported signicantly fewer transient neurological events, particularly disorders of sensation, movement, difculty speaking, and visual symptoms
(P=0.001).
Pain
146 of the patients with MS described pain at some
time in their disease course (67%). Forty-four per cent
of these patients described themselves as having active
pain problems. Though a similar percentage of
controls described themselves as having had pain,
only 22% described active pain problems (P=0.001).
The pain quality and duration varied in this population (Figures 3 and 4). Patients used a variety of
Table 1

Symptomatology of transient neurological events

Altered sensation
Altered movement
Difculty speaking
Pain
Visual symptoms
Other

Table 2

No. of

patients

patients

47
24
13
7
14
10

40
20
11
6
12
8

Description of transient events

. `Severe muscle spasms leading to cramps right side of

body'
. `Unable to move legs and feet'
. `Lose color in one eye'
. `Waves of pain across face'
. `Blurriness, like you are looking through a waterfall'
. `Vision does away completely for a few seconds, comes
back blurry'
. `Voice becomes scratchy, raspy, difcult to swallow,
coughing'
. `Vision blurry, left face twitches'
Figure 1

Duration of multiple sclerosis

Figure 2

Self-classication of multiple sclerosis type

Figure 3
controls

Pain quality in multiple sclerosis patients versus

Downloaded from msj.sagepub.com at National Dong Hwa University on April 6, 2014

Sensory symptoms of multiple sclerosis

AD Rae-Grant et al

medications for their pain, most commonly over the

counter medications. Thirty-one per cent of the MS
patients were actively using pain medications at the
time of the survey. The presence of pain was not
signicantly related to the duration of disease or the
presence of disability (P=0.54 and P=0.88 respectively). The location of pain differed between the
control group and MS group. In the control group, the
pain tended to be in the head, back and neck, while in
the MS group, pain was localized to arms, legs, trunk,
hands, feet or face signicantly more often (P=0.001)
(Table 3). In addition, pain description in controls was
predominantly throbbing, sharp or muscular, while in
the MS population pain descriptions tended to include
burning, itching, electric, and formicatory (Figure 3).
Headache
Headache was present in two-thirds of the MS patients
in this survey. Headache frequency was similar in
controls (67%), and there were no differences in
frequency or self-rated severity. One-quarter of the
patients with headache considered their headaches
`related to multiple sclerosis'. The headache frequency
varied from daily (9.6%), to every few days (12.7%),
weekly (18.5%), monthly 16.6%), every few months
(20.4%) and rarely (22.3%).
Lhermitte's phenomenon
Lhermitte's phenomenon (an `electrical' sensation
down the back or limbs with exion of the neck) is
considered characteristic of MS. Lhermitte's phenomenon was present at some time in 70% of the MS
group, and was present at the time of this survey in
55% of the patients. Interestingly, one-quarter of the
control group described a similar symptom at some
time in the past.
Respiratory symptoms
Twenty per cent of the patients (44 patients) in the
survey described the presence of respiratory symptoms. These included shortness of breath (28 patients),

Figure 4

difculty breathing deeply (18 patients), hiccups (16

patients), cough (22 patients), frequent sighing (25
patients), and `not enough air' (18 patients). Respiratory symptoms of any kind were signicantly less
frequent in the control group (7.5%, P=0.005). The
presence of respiratory symptoms did not correlate
with disability or duration of disease.
Fatigue
170 out of 224 patients (79%) described fatigue which
limited their activities. On a scale of 1 10, patients
rated fatigue ad 6.2+2.4. Signicantly fewer controls
described fatigue which limited their activity (17%,
P=0.001), and controls rated the severity signicantly
lower than the patients (3.5 versus 6.2 on severity
scale, P=0.001).
Other symptoms
'Dizziness' as a symptom was more common in the
multiple sclerosis group, occurring in 59% of the 224
patients compared with 21% of the controls (P=0.001).
Despite common descriptions of a correlation between
`sinus' infections and MS, such self-described infections were less common in the MS population than in
controls (34% versus 48%, P=0.025). Memory dysfuncTable 3

Pain location MS patients versus controls

Head
Back
Neck
Face
Arms
Hands
Trunk
Legs
Feet

Pain duration in multiple sclerosis patients versus controls

Downloaded from msj.sagepub.com at National Dong Hwa University on April 6, 2014

% MS

patients

Controls

22
32
18
14
29
35
17
67
34

42
28
27
9
14
9
3
30
14

181

Sensory symptoms of multiple sclerosis

AD Rae-Grant et al

182

tion was present in 59% of patients and 17% of

controls (P=0.001). While night time sleep did not
differ between patients and controls, restless or jumpy
legs were much more common in the patient group
(53% versus 14%). Symptoms of double vision, slurred
speech, difculty swallowing, difculty using the
hands, leg weakness, unsteady walking, and spasticity
were all more common in patients than controls.
Symptom assessment
Sensory symptoms were described as the rst symptom of MS in 43% of patients. Most stated that visual
problems were their rst symptom, with leg weakness,
gait disorder, fatigue, urinary symptoms, vertigo and
pain comprised the other responses.
Patients were asked to chose their worst symptom
from MS (Table 4). Sensory symptoms including
fatigue, urinary symptoms, vertigo, pain and paresthesias counted for 34% of the `worst symptoms' out of
total of 236 `worst' symptoms described by the
patients.
There was a signicant correlation between the total
number of sensory symptoms reported by an individual patient and the extent of disability. Thus, the
total symptom count increased with increasing disability (P40.001).

Discussion
In this survey we assessed the frequency and character
of a variety of symptoms in multiple sclerosis. Our
survey included a heterogeneous patient group with a
broad span of sub-categories of multiple sclerosis, as
well as a variety of disease duration's consistent with a
clinical spectrum of the multiple sclerosis. In this
patient population there was a signicant number of
symptom of a sensory type, representing a `hidden
reservoir' of disease morbidity.
The return rate of the survey (58%) is comparable to
that of other survey studies in the MS population.4,5
Possible reasons for the lack of a `complete' return rate
include change of address, incapacity, lack of interest,
etc. the higher rate of return in the control group was
likely due to the fact that questionnaires were handed
out and picked up in the ofces used, rather than
mailed. We reviewed the survey return rate for
medical poster questionnaires and found that a 60%
Table 4

Worst symptoms

Weak legs
Gait disorder
Visual problems
Fatigue
Urinary symptoms
Vertigo
Pain
Paresthesias
Other

No.

16
59
41
37
12
9
13
24
25

7
25
17
16
5
4
5
10
10

Total symptoms . . . 236

return rate was the expected response for this type of

study.6
Transient neurological events lasting seconds to
minutes were found in half of these patients. We are
not aware of prior assessments of the frequency of
transient neurological events in a multiple sclerosis
population. The most extensive study of transient
neurological events is that of Osterman.7 In addition,
individual case reports of transient neurological
symptoms have been published.8,9 Symptoms such as
tonic seizures, spinal sensory motor symptoms,
akinesia, dysarthria, and ataxia, hemi-ataxia with
crossed paresis, diplopia, numbness, paroxysmal pain,
cardiac dysrythmia, and paroxysmal itching have all
been described.9
Clinically, transient neurological events in MS
could be misidentied as seizures, psychogenic
phenomenon, migraine related aura, or as events
unrelated to MS. The correct identication of the
genesis and nature of these episodes may be helpful in
the care of MS patients.
Pain in this survey was a signicant feature for this
group of patients with constant pain being present in a
large percentage of the patients. Moulin et al,5
performed a review of 182 patients and sent surveys
to 159 patients. In their patient population, 55% of
patients had some type of pain. Our survey conrms
their ndings. Ramirez-Lassepas et al,10 described a
collection of patients with acute radicular pain but
made no attempt to dene the frequency of this
nding. Since pain is frequently considered an
`atypical' feature of MS, it is helpful to understand
the true frequency of this problem in a representative
patient group. In addition, the extent of over the
counter medication use should be recognized when
other medication are prescribed. The description of
pain in the study population was clinically consistent
with neuropathic pain, being more prevalent in the
limbs and face and trunk as apposed to the back and
neck, and being described by terms such as burning,
formicating, itching and electric. The proper identication of such pain as neuropathic might prompt trials of
anti-depressants or anti-epileptic medications, known
to be useful in such disorders.11
Headache has been mentioned occasionally with
multiple sclerosis but rarely assessed in terms of
frequency against a control population. Rolak et al,12
performed a survey of multiple sclerosis patients vs
patients in a general neurology clinic. They found
52% of the patients with multiple sclerosis had
headaches vs 18% of those in general neurologic
clinic. We also found headache in more than half of
the MS group, but headache was just as common in
our controls. We did not further characterize the
headache in our survey in terms of migranous vs
cluster vs muscle contraction type headache, which
may have accounted for the difference from Rolak's
study. Of interest was that our patients considered
their headache to be related to multiple sclerosis only
one-quarter of the time.
It is unclear whether this is due to their knowledge
of a separate mechanism (i.e., headache preceding
multiple sclerosis onset by signicant duration of time)

Downloaded from msj.sagepub.com at National Dong Hwa University on April 6, 2014

Sensory symptoms of multiple sclerosis

AD Rae-Grant et al

or because they had been told that there was no

association. Trigeminal neuralgia is usually mentioned
in studies of head pain in this patient population as a
more specic sensory manifestation of multiple
sclerosis.12 The general frequency of headache would
complicate analysis of `causation' related to MS in any
population studied.
Respiratory function in MS is the subject of a small
number of studies.14,15 Traditionally respiratory symptoms are considered to be a late phenomena of
multiple sclerosis associated with severe motor weakness and major disability.13 Recently Garland, et al,15
assessed patients with multiple sclerosis and found
both peripheral motor conduction abnormalities (phrenic nerve) and central conduction abnormalities in a
mild to moderately disabled group of patients (EDSS
1.5 6.5). This would suggest that subclinical respiratory efferent involvement is present in this population.
Twenty per cent of patients in our study had
respiratory symptoms, with a variety of specic
symptoms. There was no specic correlation with the
duration of disease in this population or with
disability. This was therefore not a specically `late
manifestation' nor necessarily accompanied by severe
motor weakness. It is possible that some of these
symptoms are a afferent abnormality with abnormal
respiratory sensory information. We have witnessed
young females with a sense of `air-hunger' with MS
identied as having panic disorder on the basis of
these symptoms. It appears possible that these
symptoms are a true neurologic sensory manifestation
of their disease.
Of interest was the fact that patients described their
worst symptom frequently as a symptom such as
fatigue, vertigo, paraesthesia or pain. These were the
`worst symptom' one-third of the time in this MS
group. In another mail survey of an MS population, a
similar percentage of patients had fatigue producing
ADL difculty (50% of overall sample).4 Other data
from that study included the fact that fatigue worsened
MS symptoms, was worse in warm weather, and worse
after vigorous exercise. This suggests that these
symptoms provide a signicant reservoir of morbidity
for this patient population both early and late in the
disease.
We suggest that sensory symptoms (including
transient neurological events, pain, headache, respiratory symptoms, vertigo, fatigue, Lhermitte's)
may be a signicant component of the morbidity
of multiple sclerosis independent of motor function,
visual function and objective sensory abnormalities.
It may be valuable to use these as `secondary

endpoints' for further studies of therapeutic or

clinical endeavors of multiple sclerosis as another
mechanism of assessing the quality of life in this
patient population.

Acknowledgements

We would like to thank the Neuroscience Research

group for reviewing the manuscript and for advice
on the study questionnaire. We would also like to
thank Ms Allison Hay for assisting with distribution
to the control group. This study was supported by a
grant from the Neuroscience Education Fund at
Lehigh Valley Hospital.

References
1 Kurtze JF. (1983) Rating neurologic impairment in
Multiple Sclerosis. An expanded disability scale (EDSS).
Neurology 33: 1444 1452.
2 Sipe JC et al. (1984) N neurological rating scale (NRS) in
Multiple Sclerosis. Neurology 34: 1368 1371.
3 Lublin FD, Reingold SC. (1996) Dening the clinical
course of Multiple Sclerosis: results of an international
survey. Neurology 46: 907 911.
4 Freal JE, Kraft GH, Coryell JK. (1984) Symptomatic
Fatigue in Multiple Sclerosis, ARCH. Phys Med Rehab
65: 135 138.
5 Moulin DE, Foley KM, Ebers GC. (1988) Pain syndromes
in Multiple Sclerosis. Neurology 38: 1830 1834.
6 Asch DA, Jedrziewski MK, Christauis HA. (1997)
Response Rates to Mail Surveys, Published in Medical
Journals. J CCIN EPIO 50(10): 1129 1136.
7 Osterman PO, Westerberg CE. (1975) Paroxysmal attacks
in Multiple Sclerosis. Brain 98: 189 202.
8 Koeppel MC et al. (1993) Paroxysmal pruritis and
Multiple Sclerosis. Br J Derm 129: 597 598.
9 Matthews WB. (1991) Symptoms and signs. In: McAlpine's Multiple Sclerosis 2nd ed. New York, NY pp43 77.
10 Ramirez-Lassepas M, Tulloch JW, Quinones MR, Snyder
BD. (1992) Acute radicular pain as a presenting symptom
in Multiple Sclerosis. Arch Neurol 49: 255 258.
11 Houtchens MK, Richert JR, Sami A, Rose JW. (1997) Open
label gabapentin treatment for pain in Multiple Sclerosis.
Multiple Sclerosis 3: 250 253.
12 Rolak LA, Brown S. (1990) Headaches in Multiple
Sclerosis: a clinical study and review of the literature. J
Neurology 237: 300 302.
13 Hooge JP, Redekop WK. (1995) Trigeminal neuralgia in
Multiple Sclerosis. Neurology 45: 1294 1296.
14 Howard RS et al. (1992) Respiratory involvement in
Multiple Sclerosis. Brain 115: 479 494.
15 Garland SJ, Lavoie BA, Brown WK. (1996) Motor control
of the diaphragm in Multiple Sclerosis. Muscle and
Nerve 19: 654 656.

183