Cognitive and Neuromuscular Assessment in Geriatric ... · Cognitive and Neuromuscular Assessment...
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Hala Sweed et al.
235
Cognitive and Neuromuscular Assessment in
Geriatric Patients with Thyroid Dysfunction
Hala S Sweed1, Azza A Nasser
2, Salma Khalil
2, Iman Bayomi
2
Departments of Geriatrics1, Neurology
2, Ain Shams University
ABSTRACT
The aim of this study is to evaluate objectively, the functional changes in the nervous system, central changes
(cognitive dysfunction), and peripheral changes (neuromuscular dysfunction) by using different electrophysiological
testing in Geriatric patients with thyroid dysfunction. Participants were recruited from the outpatient clinic of Geriatric
Department of Ain Shams University over a one year period. Fifteen patients with hypothyroidism and 12 patients with
hyperthyroidism, confirmed by TSH, T3, T4 level measuring and 20 control subjects matched for age and sex, were
included in the study. All participants were subjected to full neurological history and examination. Cognitive functions
assessment were done by using Mini-mental Status Examination (MMSE), and P300 long latency evoked potentials.
neuromuscular evaluation was done using sensory, and motor nerve conduction (SMNC) and electromyography (EMG).
Our results revealed presence of significant cognitive dysfunction in both hypo and hyperthyroid group of patients
compared to controls as shown by impaired MMSE and delayed P300 latency. EMG revealed no myopathic changes,
where neuropathic findings correlated with that of peripheral neuropathy. There was significant polyneuropathy mainly
axonal in both hypo and hyperthyroid groups but none in the control group. As regards the upper limbs, 75% have
sensory neuropathy and 25% motor among hyperthyroid group compared to 80% and 20% among hypothyroid group
respectively. As for the lower limbs, 75% have sensory neuropathy and 50% motor neuropathy among hyperthyroid
group compared to 60% sensory neuropathy and 60% motor neuropathy among hypothyroid group. Entrapment
neuropathy in the form of carpal tunnel syndrome was found in 25%, 20%, 20% of the hyperthyroid, hypothyroid, and
control group respectively. Conclusion: the results of our study revealed that the nervous system is vulnerable to the
effect of thyroid dysfunction both centrally and peripherally. Abnormalities included cognitive impairment,
polyneuropathy (mainly axonal) and entrapment neuropathy. (Egypt J. Neurol. Psychiat. Neurosurg., 2007, 44(1): 235-
237-250).
INTRODUCTION
Thyroid disorders are common in the elderly
and are associated with significant morbidity if left untreated. Typical symptoms may be absent and may be erroneously attributed to normal aging or coexisting disease
1. Manifested hypothyroidism and
hyperthyroidism have long been known to cause mental and neurological dysfunction
2. Both
hypothyroidism and hyperthyroidism may cause signs and symptoms of neuromuscular dysfunction. Hypothyroidism has been associated with the clinical features of myopathy
3 (for example, proximal muscle
weakness), mononeuropathy, and sensorimotor axonal polyneuropathy
4. Hyperthyroidism may also
cause myopathy5 and possibly also polyneuropathy
6.
The reported prevalence of these signs and symptoms is variable.
In retrospective studies7A
, published in the
early1980s, the prevalence of neuropathy in
hypothyroid patients varied between 10% and
70% and that of myopathy between 20% and
80%, whereas the prevalence of myopathic
features in hyperthyroidism varied between 60%
and 80% of the patients5. Concerning the
cognitive function, hyperthyroidism was found to
cause dementia like symptoms8. Hypothyroidism
was also found to be associated with defective
memory, psychomotor slowing and depression9.
The aim of this study is to evaluate
objectively, the functional changes in the nervous
system, both central (cognitive dysfunction), and
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peripheral (neuromuscular dysfunction) among
elderly patients with thyroid disease.
METHODOLOGY
Subjects:
All elderly patients 60 years old and over
with newly diagnosed thyroid dysfunction
(abnormal serum concentrations of thyroid
stimulating hormone (TSH) and free thyroxine
(FT4),and (FT3)) attending the outpatient clinic of
the Geriatrics department of Ain Shams
University Hospitals over a one year period(
1/12/2004 -1/12/2005) were recruited for our
study. An age and sex matched group of controls
(normal serum concentrations of thyroid
stimulating hormone (TSH) and free thyroxine
(FT4)),(FT3) was also included in the study.
Inclusion criteria
(1) Newly diagnosed hypothyroidism or
hyperthyroidism patients, and (2) older than 60
years for both cases and controls.
Exclusion criteria
(1) other possible causes of neuropathy or
neuromuscular diseases(for example, diabetes
mellitus, alcoholism, liver and kidney disease, use of
drugs known to cause neuropathy or myopathy,
malignancy, or other serious illness (for example,
cardiac failure), a family history of neuropathy), and
(2) pre-existence myopathy or neuropathy, (3) No
history suggestive of cerebrovascular insult (Stroke,
or TIA), (4) No vascular insult were detected in their
brain neuroimaging.
All participants were subjected to comprehensive
geriatric assessment including:
* Clinical neurological history and examination
Full neurological examination with special
emphasis on individual muscle examination
to assess the power of the major muscle
groups e.g. (neck flexors and extensors,
shoulder elevators and abductors, elbow
flexors and extensors, wrist flexors and
extensors, hand grip; flexors, adductors and
abductors of the hip, knee flexors and
extensors, foot dorsi and plantar flexors) and
sensory system examination.
* Mini-mental status examination (MMSE)10
,
Arabic version11
was used for assessment of
cognitive function. The MMSE comprises 30
questions with 10 devoted to orientation (five
regarding time and five regarding place); three
items requiring registration of new information
(repeating three words), five questions
addressing attention and calculation (mental
control questions requiring patient to make five
serial subtractions of 7 from 100 or spell word
backward), three recall items (remembering the
three registration items), eight items assessing
language skills (two naming items, repeating
phrase, following a three-step command,
reading and following a written command and
writing a sentence), and one construction
question (copying a figure consisting of two
overlapping pentagons). A score less than 24/30
indicates cognitive impairment.
* Investigations done for patients to fulfill the
inclusion and exclusion criteria included;
(complete blood count, liver and renal function
tests, measurement of electrolytes, and
sedimentation rate, and brain neuroimaging).
* The objective functional cognitive change
was assessed electrophysiologically using
the long latency P300 evoked potentials.
Recordings of P300 Long Latency evoked
potentials were made in a sound attenuated
room with subject seated in a reclining chair.
Bipolar recordings were made between silver-
to-silver chloride electrodes at three midline
sites: frontal (FZ), central (CZ) and parietal
(PZ), according to the 10- 20 electrode system
of the International Federation. A ground
electrode was positioned at FPZ and indifferent
ear - clip electrodes were attached to both ear
lobules. The electrode impedance was less than
2 kilo – ohms.
Sounds were delivered binaurally through
headphones. Tones were presented in a random
sequence. Eighty five percent of the stimuli
(frequency) were low-pitched tones of 1000 Hz
and 50 milliseconds duration. The other fifteen
percent of the stimuli (oddball) were high-
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pitched tones of 2000 Hz and 50 milliseconds
duration. The ratio of high to low pitched tones
was 1 : 10 / sec. Intensity was 60 dB above
hearing level (SPL) with a rise - fall time of 10
milliseconds. The EEG was amplified by 10000
(2 MK Counterpoint - Dantec amplifier) and
the response of frequent and rare tones were
averaged separately. We used a bandwidth of
0.5- 40 Hz and a sensitivity of 20 UV.
A total of 500 epochs were averaged and
data was monitored by a software procedure as
it was sampled, and any data containing high
voltage artifacts was automatically reflected.
Prior to processing, all data were smoothed
with a bi-directional digital filter.
Latencies and baseline - to - peak
amplitudes of the individual components of
the (Evoked response potential) ERP curve
were measured. These were designated N1,
P2. N2, and P3.
N1 (N100) was the point of maximum
negativity between 70 - 120 msec and P2
(P200) the maximum positive deflection
between 140 - 230 msec in the average
response to frequent stimuli. P3 (P300) was
the positive wave deflection between 265
and 500 msec in the averaged response in the
rare stimuli and N2 (N200) was the negative
deflection immediately preceding P3.
Latencies were measured at the point of
maximum amplitude for each component
using a cursor on the Counterpoint - Dantec
visual display unit and by inspection of the
pen-recorded trace. When the deflection did
form a single sharp wave, the latency was
measured at the point of intersection of the
tangents to the upgoing and downgoing
slopes measured from pen-recorded trace.
Subjects were instructed to count
silently high pitched tones and report at the
end of the trial how many high pitched tones
they had heard. No task was assigned to the
subjects.
* The functional peripheral changes were
assessed neurophysiologically using EMG
and NC Studies. EMG & NC Studies were
done by using (2 MK-Conterpoint-DANTEK
amplifier).
EMG studies (concentric needle EMG)
were performed in the upper limbs (ULs) in the
flexor pollicis brevis representing distal muscles
(ms) of the UL & the deltoid & biceps ms. In
the lower limbs (LLs), extensor digitorum
brevis (distal ms) was studied as well as the
quadriceps femoris proximally. Amplitude &
duration of motor unit potentials were recorded
during moderate voluntary muscle contraction.
Interference pattern of motor unit potentials
(MUPs) was recorded during maximal
voluntary muscle contraction to verify
myogenic versus neurogenic affection.
* Nerve conduction studies were performed using
bipolar stimulating surface electrodes, held in
2.5 cm apart and arranged so that the active
electrode was closer to the recording electrode.
A. Motor nerve conduction studies were
done to the left ulnar, and right median
nerves in upper limbs and Right common
peroneal and Left posterior tibial nerves
in lower limbs.
The median nerve was stimulated at
wrist and at the elbow and the response
recorded from the thenar muscles. The
ulnar nerves was stimulated at the wrist
and behind medial epicondyle of the
humerous and motor evoked potentials
was recorded by means of surface
electrodeds were placed over hypothenar
muscles. The common peroneal nerve
was stimulated above the ankle and
behind the head of fibula and the motor
evoked potentials were recorded from the
extensor digitorum brevis muscle. The
posterior tibial nerve was stimulated
behind the medial malleoulas, and politeal
fossa and the response was recorded from
the abductor hallucis muscle.
The motor latencies were
measured at sites of stimulation of the
above mentioned nerves. Motor nerve
conduction velocity (MCV) was
calculated, it is the time along the
segment of the nerve between two
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stimulated sites, the motor evoked
potentials recorded after supramaximal
stimulation at proximal and distal sites
and were analysed for latency (which is
measured from stimulus site to the
onset of 1st deflection in seconds) and
the amplitude in (mv).
B. Sensory nerve conduction studies
(SNCS):
Sensory nerve conduction of the left ulnar
and right median in upper limbs and left
or right sural nerve in the lower limbs
were studied, the SNC latency measured
from to the first negative peak of
compound action potentials. The sensory
active electrode applied over the index
finger to record sensory potential
antidromically of the median nerve and
applied over the 5th digit for ulnar nerve
sensory potential and behind the lateral
malleaous for sural sensory action
potential and the reference electrode
placed 2.5 cm apart distally.
The measurements of distal
latency (DL), conduction velocity
(CV), and amplitude of studied motor
and sensory nerves are considered
abnormal if they were more than two
standard deviations below the control
group, and accordingly classified to
axonal neuropathy if there is significant
diminish in amplitude and
demyelinating lesion manifested by low
CV and delayed DL, and entrapment
neuropathy in the form of (carpal
tunnel syndrome) when there is median
nerve distal latency affected12
.
The peripheral neuropathy is
defined by presence of two of the
following: (1) neurological symptoms
consistent with a distal symmetrical
polyneuropathy, (2) neurologic signs
consistent with distal symmetric
neuropathy, (3) abnormal objective nerve
function test in at least two nerves13
.
Data processing & statistical analysis:
Data collected were revised, coded,
tabulated & introduced to PC for statistical
analysis. All data manipulation & analysis were
performed using the 11th
version of SPSS
(Statistical Package for Social Sciences).
Qualitative data is presented in form of frequency
tables (numbers and percent), while quantitative
data is presented in form of mean±standard
deviation. The statistical tests used included;
independent sample-t test, and Chi-square test.
RESULTS
After the application of the exclusion
criteria, the study included 47 participants; 15
hypothyroid cases, 12 hyperthyroid cases and 20
participants as their controls. They were all
females. The mean age of the studied group was
69.06±7.54 with no statistical difference between
the control group (mean age=68.10±7.03) and the
hypothyroid group (mean age= 67.60±8.99,
t=0.185, p=0.854), and the hyperthyroid group
(mean age =72.50±5.65, t=1.838, p=0.076).
Duration of symptoms of thyroid dysfunction
among hypothyroid group was 10.00±1.69 months
versus 10.58±2.68 among hyperthyroid group
(t=0.691, p=0.49).
Concerning the neurological symptoms and
signs found, there was statistically significant
difference between the hypothyroid group and the
control group in the frequency of abnormal sensation
(X2=6.022, p=0.014), burning sole (X2=16.154,
p=0.000), lower limb peripheral neuropathy (stoking
hypothesia) (X2=16.154, p=0.000), but not in the
frequency of wrist pain related to carpal tunnel
syndrome (X2=0.000, p=1.000), and upper limb
peripheral neuropathy (glove hypothesia) (X2=1.680,
p=0.195) (Table 1).
As for the hyperthyroid group, there was
statistically significant difference with the control
group in the frequency of decreased sensation
(X2=9.877, p=0.02), burning sole (X
2=12.308,
p=0.000), upper limb and lower limb peripheral
neuropathy (X2=9.406, p=0.002, X
2=12.308,
Hala Sweed et al.
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p=0.000 respectively), but not in the frequency
of wrist pain (X2=3.142, p=0.076).
Significant difference was found between the
control group and the hypothyroid group (t=5.050,
p=0.000) but not with the hyperthyroid group
(t=1.747, p=0.091) concerning the MMSE score,
still, with lower MMSE score among both the
hypothyroid and the hyperthyroid groups. Significant
delay in P300 latency was found in both the
hypothyroid and the hyperthyroid group in compare
to the control group with the difference statistically
significant for the hypothyroid (t=4.505, p=0.000)
and the hyperthyroid group (t=2.646, p=0.013) as
shown in (Table 2).
Higher frequency of cognitive impairment
among the hypothyroid and hyperthyroid groups,
was found to be 80% (n=12) and 41.7% (n=5)
respectively, compared to 20% (n=4) among the
control group, yet, statistically significant
difference was found between the control group
with the hypothyroid group (X2=12.434,
p=0.000), but not with the hyperthyroid ones
(X2=1.742, p=0.187) (Fig. 1).
40% (n=8) had delayed latency among
control group compared to 80% (n=12) and 75%
(n=9) among the hypothyroid group (X2=5.600,
p=0.018) and hyperthyroid group respectively
(X2=3.689, p=0.055) (Fig. 2).
In comparing patients without cognitive
impairment (MMSE ≥24) with the control group the
delay in p300 latency was statistically significant
comparing controls with hypothyroid patients
(t=2.998, p=0.008) and just insignificant with
hyperthyroid ones (t=1.962, p=0.063) (Table 3).
None of the studied group was found to have
myopathic pattern of affection, but 40% (n=6) of
hypothyroid group (X2=9.655, p=0.002) and 50%
(n=6) of hyperthyroid group (X2=12.308,
p=0.000) had neurogenic patterns (Table 8).
The motor axonal neuropathy, was present in
upper limbs in 20% (n=3) of the hypothyroid
patients and 60%(n=9) in the lower limb
(X2=4.375, p=0.036, X
2=16.154, p=0.000
respectively). Also, 25% (n=3) of the
hyperthyroid patients were having motor axonal
neuropathy in the upper limb, and 50% (n=6) in
the lower limb (X2=5.517, p=0.019, X
2=12.308,
p=0.000 respectively) (Table 8).
As regard the demyelinating neuropathy
there was significant demyelination in the LLs
40% (n=6)P0.002 in the hypothyroid group, and
50% (n=6) P0.000 in the hyperthyroid group.
Sensory neuropathy, in the upper limbs was
present in 80% (n=12) of the hypothyroid
group(X2=24.348, p=0.000) and 75% (n=9) of the
hyperthyroid group(X2=20.870, p=0.000). As for
the lower limb, 60% (n=9) of the hypothyroid
group (X2=4.375, p=0.036) and 75% (n=9) of the
hyperthyroid ones (X2=7.619, p=0.006) were
having sensory neuropathy..
There was no statistical significant difference
between the control group and either the hypothyroid
group (X2=0.000, p=1.000) or the hyperthyroid
group (X2=0.110, p=0.740) concerning the
frequency of entrapment neuropathy, with the
frequency being, 20% (n=4), 20% (n=3), and 25%
(n=3) among the controls, hypothyroid group and
hyperthyroid group respectively.
Illustrating Examples:
Case 1: A Case of Hyperthyordism
Motor Nerve Conduction of right median
nerve shows normal study (Fig. 1).
Motor Nerve Conduction of left posterior
tibial nerve and EMG Study of the left abductor
hallucis muscle shows neurgenic pattern ,and
mixed axonal ,and demyelinating neuropathy in
the left posterior tibial nerve (Figs. 2, 3, 4).
Brainstem auditory P300 study, shows
normal latency denoting no affection of cognitive
function (Fig. 5).
Case 2: A Case of Hypothyrodism
Motor nerve conduction of left ulnar shows
normal nerve conduction study (Fig. 6).
Motor Nerve Conduction of left posterior
tibial nerve and EMG Study of the left abductor
hallucis muscle, shows neurgenic pattern and
axonal neurapathy in the left posterior tibial nerve
(Figs. 7, 8, 9, 10).
Egypt J. Neurol. Psychiat. Neurosurg. Vol. 44 (1) - Jan 2007
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Brainstem auditory P300 study shows
delayed latency of P300 denotes cognitive
impairment (Fig. 11).
Table 1. Comparison of the sensory symptoms and signs presentation among the three studied groups.
Hypothyroid
N=15
Control
N=20
Hyperthyroid
N=12
N % N % N %
Symptoms: Wrist pain Abnormal sensation in either ULs or LLs or both Burning sole
3 4 9
20
26.7 60
4 0 0
20 0 0
6 5 6
50
41.7 50
Signs: UL peripheral neuropathy(glove hypothesia) LL peripheral neuropathy(stoking hypothesia)
6 9
40 60
4 0
20 0
9 6
75 50
Table 2. Results of cognitive function assessment using MMSE and P300 among the studied groups.
Hypothyroid N=15
Control N=20
Hyperthyroid N=12
Mean±SD Mean±SD Mean±SD
MMSE 16.60±7.25 25.10±1.86 22.42±6.50
P300 366.80±44.61 317.50±17.78 343.75±38.30
MMSE = mini-mental status examination scale.
Hyperthyroid group
Hypothyroid group
Control group
Number
0f
subjects
18
16
14
12
10
8
6
4
2
0
COGNTVE
normal
impaired
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Fig. (1): the frequency of cognitive impairment among the studied groups diagnosed
by MMSE where the cognitive impairment was more in the hypothyroid group.
Fig. (2): The frequency of delayed latency using P300 among the studied groups
where there is more significant delay in the hypothyroid group.
Table 3. Comparison between the P300 latency of the three groups according to the presence of cognitive
impairment by MMSS.
Hypothyroid
N=15
Control
N=20
Hyperthyroid
N=12
Mean±SD Mean±SD Mean±SD
Patients without cognitive
impairment MMSE (≥24) 322.00+0.00 311.13±11.78 325.57±24.03
Table 4. Sensory conduction studies among hypothyroid group and control group.
Nerve Parameter DL
Hypo Control
Lt U Value 4.25 ± 0.39 2.53 ± 0.25
Significance t=15.759 p=0.000
Rt Med Value 4.78 ± 2.73 2.80 ± 0.25
Significance t=3.246 p= 0.003
Hyperthyroid Group
Hypothyroid Group
Control Group
Number Of
subjects
14
12
10
8
6
4
2
0
LATENCY
normal
delayed
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Sural Value 6.90 ± 2.13 5.10 ± 0.95
Significance t=3.983 p= 0.000
P < 0.05 significant
Table 5. Sensory conduction studies among hyperthyroid group and control group.
Nerve Parameter DL
Hyper Control
Lt U Value 4.01±0.53 2.53±0.25
Significance t=10.664 p= 0.000
Rt Med Value 4.50±0.82 2.80±0.25
Significance t=8.645 p= 0.000
Sural Value 6.50±0.98 5.10±0.95
Significance t=3.366 p=0.002
Table 6. Motor nerve conduction studies among hypothyroid group and control group.
Nerve Parameter DL Amp CV
Hypo Control Hypo Control Hypo Control
Lt U Value 2.62±0.12 2.53±1.16 7.32 ± 2.42 5.64±1.68 56.14±9.51 58.21±5.06
Significance t=0.282 p= 0.780 t=2.429 p= 0.021 t= 0.834 p=0.410
Rt
Med
Value 3.80±0.41 3.88±0.55 5.82 ± 3.13 7.29±1.91 50.54±4.99 55.50±5.91
Significance t=0.471 p=0.641 t=1.726 p=0.094 t=3.451 p= 0.002
Rt CP Value 6.24±1.73 5.50±0.40 1.01 ± 0.47 5.05±1.35 38.00±4.41 42.40±4.59
Significance t=1.857 p=0.072 t=11.070 p= 0.000 t=3.975 p= 0.000
Lt PT Value 6.06±1.55 3.62±0.61 3.07 ± 2.68 5.80±1.35 37.78±3.28 49.18±4.88
Significance t=6.413 p= 0.000 t=3.935 p=0.000 t=7.812 p= 0.000
P < 0.05 significant, Lt U Left Ulnar, Rt Med Right Median, Rt CP Right Common peroneal,
Lt PT Left Posterior Tibial, DL Distal Latency (m sec), CV Conduction Velocity (m/sec), Amp Amplitude (m v)
Table 7. Motor nerve conduction studies among hyperthyroid group and control group.
Nerve Parameter DL Amp CV
Hyper Control Hyper Control Hyper Control
Lt U Value 3.25±0.28 2.53±1.16 7.27±2.62 5.64±1.68 59.15±3.89 58.21±5.06
Significance t=2.088 p= 0.045 t=2.161 p=0.039 t=0.549 p=0.587
Rt
Med
Value 3.80±0.45 3.88±0.55 4.12 ± 1.79 7.29±1.91 46.10 ± 4.66 55.50±5.91
Significance t=0.701 p=0.489 t=4.641 p= 0.000 t=4.691 p= 0.000
Rt CP Value 5.82±1.03 5.50±0.40 0.87 ± 0.53 5.05±1.35 41.67 ± 6.96 42.4 0±4.59
Significance t=1.276 p=0.212 t=10.215 p=0.000 t=0.356 p=0.724
Lt PT Value 5.47±0.58 3.62±0.61 2.60 ± 0.92 5.80±1.35 40.60 ± 1.32 49.18±4.88
Significance t=8.391 p= 0.000 t=7.119 p= 0.000 t=5.930 p= 0.000
P < 0.05 significant, Lt U Left Ulnar, Rt Med Right Median, Rt CP Right Common peroneal,
Egypt J. Neurol. Psychiat. Neurosurg. Vol. 44 (1) - Jan 2007
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Lt PT Left Posterior Tibial, DL Distal Latency (m sec), CV Conduction Velocity (m/sec), Amp Amplitude (m v)
Table 8. The frequency interference pattern changes and neuropathy according to EMG and NC studies of the
three groups.
Hypothyroid
N=15
Control
N=20
Hyperthyriod
N=12
N % N % N %
Reduced interference pattern (neurogenic) 6 40 0 0 6 50
Motor Axonal neuropathy
UL Median nerve 3 20 0 0 3 25
Ulnar nerve 3 20 0 0 3 25
LL CP 9 60 0 0 6 50
PT 9 60 0 0 6 50
Demyelinating Motor Neuropathy LL PT 6 40 0 0 6 50
Sensory neuropathy UL
Median nerve 12 80 0 0 9 75
Ulnar nerve 12 80 0 0 9 75
LL Sural nerve 9 60 0 0 9 75
Enterapment neuropathy 3 20 4 20 3 25
Fig. (1): Shows a Normal Latency and
Conduction Velocity.
Fig. (2): Shows Delayed Latency and Conduction
Velocity with Low Amplitude.
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Fig. (3): Shows increased duration and average amplitude of motor unit
potential (neurogenic pattern) with polyphasia.
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244
Fig . (4): Shows Reduced Interference Pattern (neurogenic pattern).
Fig. (6): Shows a normal latency and
conduction velocity.
Fig. (5): Shows normal P300 latency.
Fig. (7): Shows delayed latency and normal conduction
velocity with low amplitude.
Hala Sweed et al.
245
Fig. (8): Shows no resting activity.
Fig. (9): Shows increased amplitude average
duration of motor unit potential with polyphasia
Fig. (10): Shows reduced interference pattern.
Fig. (11): Shows delayed P300 latency.
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246
DISCUSSION
Thyroid dysfunction often presents with non
specific symptoms in the elderly14
. Physiological aging
induce changes of the hypothalamic pituitary axis, yet,
slight decrease in the TSH, and free tri-iodothyroxin
(T3) level have been described to occur normally in the
healthy elderly persons15
. It was found that as one ages
there are certain changes undergoes within the thyroid
gland itself e.g. fibrous tissues increases, macro-micro
nodules develop and the thyroid gland itself fail to
maintain the euthyroid state15
. Thyroid disorders,
especially in the elderly are commonly associated with
complains related to the nervous system, whether
central or peripheral. Thyroid hormones have critical
role in normal brain function, there is clinical evidence
suggests that human nervous system disorders involving
GABA(gamma aminobutyric acid) are related to thyroid
dysfunction(hyper or hypothyroidism),and that there is
reciprocal regulation of the thyroid GABA system16
.
Li et al.17
reported that thyroid hormones are
essential for the maturation and repair of the
peripheral nervous system which has its own system
responsible for local production of 3,5,3
triiodothyronine, which play a role in the
regeneration process.
The relationship between the thyroid status and
cognitive disturbances remains unclear9, in our study the
results of MMSE score revealed presence of significant
cognitive impairment among the hypothyroid group
compared to the control group (Table 2, Fig 1) which
corresponds to the early study of Osterweil et al 18
in
which it was reported that the MMSE itself was
sensitive in differentiating hypothyroid group of patients
with cognitive deficits from the control group. Also, the
frequency of cognitive impairment was more among the
hyperthyroid group than the controls, yet not statistically
significant (Table 2, Fig. 1). Li et al.8, recommended
that dementia like symptoms secondary to
hyperthyroidism should be kept in mind as one cause of
treatable dementia. Also, Sait Gönen2 stated that the
manifest (overt) hypothyroidism and hyperthyroidism
causes mental and neurological dysfunction.
Using the P300 long latency evoked potentials
measuring as an objective neurophysiological method
for assessing the cognitive function, the results of our
study revealed presence of significant delay in P300
latency in both hypo and hyperthyroid group of patient
but more delay in the hypothyroid group denoting
presence of cognitive dysfunction in both groups more
in the hypothyroid one (Table 2, Fig. 2). Tutuncu et al.19
,
reported that P300 delay latency was found in both mild
and sever cases of hypothyroidism, even in those with
normal MMSE score, significant delay in P300 latency
was found among the hypothyroid and hyperthyroid
groups compared to the control group as proved in our
study and shown in table (3).
As for the peripheral nervous system, this
study showed that many patients with thyroid
problems have neuromuscular findings, as
manifested by neurophysiological assessment
through EMG and NC studies.
As regard the sensory manifestations presented
in those patients. Many patients have sensory
complaints either diminished sensation or burning
sensation (specially the soles). Also, several signs
were found among the participants including
peripheral neuropathy. These complaints and signs
were more frequent among both case groups
compared to controls (table 1). These findings were
correlated to those of Donofrio and Albers20
, who
found that sensory signs may predominate and may
be at an earlier phase of the disease.
Nerve conduction studies revealed sensory
neuropathy in the hyperthyroid group of patients,
75% of them in UL (Table 8) as evidenced by
significant delayed latency of the Lt ulnar, and the
Rt median nerve (Table 5). (This percentage exceeds
the motor neuropathy in UL 25% only) and also the
75% of patients have sensory neuropathy in LLs
(Table 8) as evidenced by significant delayed latency
of the sural nerve (Table 5).
While in hypothyroid group of patients the
sensory neuropathy was detected in 80% of patients
in ULs (Table 8) denoted by significant delayed
latency of the Lt ulnar, and the Rt median nerves
(table 4) while 60% of sensory neuropathy in LLs
(table 8),as denoted by significant delay in latency of
the sural nerve (Table 4). These percentages of
sensory neuropathy were higher than what was
found by Khedr et al.21
, which reached 9% only of
cases. But in other studies published in the early
1980s, the prevalence of sensory neuropathy in
hypothyroid patients varied between 18% and
70%3,7A
.
On the other hand, the EMC studies have
correlated to the finding of peripheral neuropathy.
Egypt J. Neurol. Psychiat. Neurosurg. Vol. 44 (1) - Jan 2007
248
Neurogenic pattern was found in 50% of patients
with hyperthyroidism and 40% of patients with
hypothyroidism, this showed a significant value on
comparison between groups (Table 8). In support of
our findings Duffy et al.22
, found that 17% of
hypothyroid patients had neurogenic changes in the
EMC while 24% of hyperthyroid patients had these
changes.
In spite of our findings, other studies showed
the myopathic pattern of affection to be detected as
found by Rao et al 3 and Khaleeli et al.
7B, between
20% and 80% in hypothyroid group of patients.
Also, Duffy et al.22
found the myopathic pattern of
affection in 33% of hypothyroid patients. In
hyperthyroidism Puvanendran et al 5 detected
myopathy in 80% of patients while Duffy et al.22
found it to be 10%.
Such assessment in patients with
hyperthyroidism revealed evidence of motor
neuropathy in the upper limb of axonal type as
evidenced by significant decrease in amplitude of
the left ulnar, and Rt median nerves (Table 7). The
prevalence of affection in hyperthyroid group was
significant and was found in 25% of cases (Table 8).
This percentage was 20% among the hypothyroid
group. Axonal neuropathy in lower limbs also was
detected (as evidenced by significant decrease in
amplitude of the Rt CP, and Lt PT nerves (Table 6),
was also statistically significant with the percentage
being 50% and 60% among the hyperthyroid and the
hypothyroid groups respectively (Table 8). The
finding of significant axonal neuropathy in
hyperthyroid patients in both upper and lower limbs
had not been supported by earlier studies6,23
,
although more recent study by Duffy et al 22
found a
significantly high incidence of axonal neuropathy in
hyper thyroid patients, 19%, which is rather in
accordance with our findings. Duffy et al.22
also
found that hypothyroidism group of patients show
axonal neuropathy in 60% (p = 0.00), while the
tarsal tunnel entrapment neuropathy in 20% with
significance 0.03.
Also entrapment neuropathy of the median
nerve has been observed in 25% of hyperthyroid
patients and 20% of hypothyroid patients though
such a finding was statistically insignificant when
compared to controls (Table 8). This finding differs
from what had been observed by DeKorn et al.24
,
who found the incidence of entrapment neuropathy
in those patients to be as low as 5%. Other studies
done by Khedr et al.21
found 35% of hypothyroid
patients to have entrapment neuropathy while Duffy
et al.22
found 25% of hypothyroid patients had
entrapment neuropathy
Regarding demyelinating neuropathy in the
upper limb, there has been no report in such
category of thyroid dysfunction contrary to what has
been found in lower limb where the incidence was
40% -50% in the hypothyroid, and the hyperthyroid
group respectively which is statistically significant
(Table 8) which is proved by presence of significant
delay latency ,and decrease in CV in the PT nerve in
both the hypo, and hyper thyroid group (Tables 6
and 7) in the study of Duffy et al.22
found that
hypothyroidism group of patients show
demyelinating neuropathy in 40% with a significant
p value 0.02.
The results of our study revealed presence of
significant decrease in CV of the Rt median nerve in
the hypothyroid group (Table 6), and significant
delay latency in the Lt ulnar nerve in the
hyperthyroid group (Table7) which could be
explained by the presence of early demyelinating
neuropathy as the finding don’t meet the criteria of
demyelinating neuropathy25
where there should be
both belay in latency, and decrease in CV in two or
more of the studied nerves.
The current study also revealed presence of
significant decrease CV in the Rt CP nerve in the
hypothyroid group (Table 6), and in the Rt median
nerve in the hyperthyroid group (Table 7) these
finding together with the presence of significant
diminish amplitude of both nerves (Tables 6 and 7)
interpreted by in the presence of severe affection of
large diameter axon, the motor CV can fall
markedly, while early in the disease the CV in
surviving axons will be normal or marginally
reduced26
.
So we conclude from the electrophysiological
NC, and EMG studies that there is mixed axonal
degeneration and demyelinating form of neuropathy
but the study fulfilling the criteria of axonal
degeneration with early mild demyelination process.
We conclude from the current study that sensory
symptoms and signs occur frequently in newly
diagnosed patients with thyroid dysfunction in geriatric
population with predominant sensory signs and sensory
nerve conduction study abnormalities early detected in
both upper and lower limbs which could be resolved on
thyroid hormone replacement therapy. As regard, the
Hala Sweed et al.
249
cognitive dysfunction, it is increasingly important that
in geriatric population, careful medical evaluation
should be done to all cases presented with early
symptoms of dementia to exclude thyroid dysfunction,
and the other treatable causes of cognitive impairment.
The impact of subclinical disturbances in
thyroid function in the elderly and laboratory
screening for thyroid dysfunction in patients over
age 65 are recommended in further studies.
REEFRENCES
1. Rehman S. U., Cope D. W., Senseney A. D.,
Brezezinski W.: Thyroid Disorders in Elderly
Patients. South Med J, 2005 May; 98(5): 543-9.
2. Sait Gönen M., Kisalko G., Savas Cilli A.,
Dikbaso, Gungor K., Inal A., Kaya A.:
Assessment of anxiety in Subclinical Thyroid
Disorders. Endoc J. 2004, 51(3): 311-5.
3. Rao SN, Katiyar BC, Nair KRP, et al (1980):
Neuromuscular status in hypothyroidism. Acta
Neurol Scand 61: 167-77.
4. Nemni R, Bottacchi E, Fazio R, et al (1987):
Polyneuropathy in hypothyroidism: clinical,
electrophysiological and morphological findings
in four cases. J Neurol Neurosurg Psychiatry 50:
1454-60.
5. Puvanendran K, Cheah JS, Naganathan N, et al
(1979): Thyrotoxic myopathy. A clinical and
quantitative analytic electromyographic study. J
Neurol Sci 42: 441-51.
6. Sözay S, Gökçe-Kutsal Y, Celiker R, et al (1994):
Neuroelectrophysiological evaluation of
untreated hyperthyroid patients. Thyroidol Clin
Ex 6: 55-9.
7A. Khaleeli AA, Griffith DG, and Edwards RH
(1983): The clinical presentation of hypothyroid
myopathy and its relationship to abnormalities in
structure and function of skeletal muscle. Clin
Endocrinol 19: 365-76.
7B. Khaleeli A. A., Gohil K., Me-Phail G., et al:
Muscle Morphology and Metabolism in
Hyperthyroid Myopathy: Effects of Treatment. J
Clin Pathol 1983; 36: 519-26.
8. Li Y., Ohira, Nartia Y., Kuzuhara S.: Transient
Dementia During Hyperthyroidism of Painless
Thyroiditis. A Case Report. Rinsho Shinkeigaku.
2003; 43(6): 341-4.
9. Constant El., Devolder A. G., Ivanoiu A., Bol A.,
Labar D., Seghers A., Cosnard G., Melin J.,
Daumeniec: Cerebral blood flow and glucose
metabolism in hypothyroidism: a positron
emission tomography study. J Clinical Endocirnol
Metab. 2001 August; 86(8): 3864-70.
10. Folstein MF, Folstein SE and McHugh PR
(1975): “Mini-Mental State”: a practical method
for grading the cognitive state of patients for the
clinician. J Psychiatr Res; 12:189-198.
11. El-Okl MA, El-Banouby MH, El-Etribi MA, et al
(2002): Prevalence of Alzheimer disease and
other types of dementia in the elderly. MD
Thesis. Ain Shams University: Geriatrics
Department Library.
12. Kimura J.: Assesment of Individual Nerve.
Electro Diagnosis in Diseases of Nerve and
Muscle: Principles and Practice, 2nd ed. Kimura
J. (ed) F. A. Davis Company, Philadelphia 1989.
13. D. A. Greene, MD; J. C. Arezzo, Ph.D.; M. B.
Brown, Ph.D.; and the Zenarestat Study Group:
Effect of Aldose Reductose Inhibition on Nerve
Conduction and Morphometry in Diabetic
Neuropathy: Neurology 1999; 53: 580-590.
14. Weissel M.: Thyroid Dysfarction in Aged
Persons. Wien Med Wochenschr. 2005; 155(19-
20): 458-62.
15. Weissel M.: Disturbances of Thyroid Function in
the Elderly. Wein Klin Wochenschr. 2006;
118(1-2): 16-20.
16. Weins SC; Trudeau VL .Thyroid hormone and
gamma-aminobutyric acid (GABA) interactions
in neuroendocrine systems.Comp Biochem
Physiol .2006;144(3): 332-44.
17. Li W., Le GoascogneC,Schumacher M,Pierre
M,CourtinF.Type 2 deiodinase in the peripheral
nervous system: induction in the sciatic nerve
after injury. Neuroscience. 2001; 107(3):507-18.
18. Osterweil D., Syndulko K., Cohen S. N., Pettler –
Jennings P. D., Hershman J. M., Cummings J. L.,
Tourtellotte W. W., Solomon D. H.: Cognitive
Function in non-demented Older Adults with
Hypothyroidism. J. Am Geriatr Soc. 1992 Apr;
40(4): 325-35.
19. Tutuncu N. B., Karatas M., Sözay S.: Prolonged
P300 Latency in Thyroid Failure: A Paradox -
P300 Latency Recovers Later in Mild
Hypothyroidism than in Severe Hypothyroidism.
Thyroid 2004 Aug.; 14(8): 622 – 7.
20. Donofrio P. D., Albers J. W., AAEM
minimonograph 34: Polyneuropathy: Classification
by nerve Conduction Studies and Electromyography,
Muscle Nerve 1990; 13: 889-903.
21. Khedr E. M., El Toomy L. F., Tarkhan M. N.,
Abdelal G (2000).: Peripheral and Central Nervous
Egypt J. Neurol. Psychiat. Neurosurg. Vol. 44 (1) - Jan 2007
250
System Alterations in Hypothyroidism Electro
Physiological Findings. Neuropshycholobiology
Jan; 41(2): 88-94.
22. Duffy R. F., Van Den Bosch J, Lamar D. M., Van
Loon B. J., Linssen W. H.: Neuromuscular Findings
in Thyroid Dysfunction. A Prospective Clinical and
Electrodiagnostic Study. J Neuro/Neurosurg
Psychiatry. 2000 Jun; 68(6): 750-5.
23. Berlin P., Mahlberg U., Usadel K. H., Zun Frage
der Polyneuropathie bei Hyperthyease Eine
Klinisch – Neurophysiollogishe Sudie. Schwi 2
Arch Neuro Psych. 1992; 143: 81 – 90.
24. DeKorn MCTFM, Knipschild T. G., Kester
ADM, et al Carpal Tunnel Syndrome: Prevalence
in the General Population. J clin Epidemiol 1992;
45: 373-6.
25. Ad Hoc Subcomittee of American Academy of
Neurology AIDS Task Force (1991). Research
Criteria for Diagnosis of Chronic Inflammatory
Demyelinatring Polyneuropathy (CIDP).
Neurology, 41, 617-18.
26. Cornblath, D. R., Kuncl, Row, Merlits, E.D. et al
(1992). Nerve Conduction Studies in Anytrophic
Lateral Silerusis. Muscle and Nerve, 15, 1111-15.
ــص العربـــىخالمل
تقويم الوظائف المطرفيه و الجوانب الطصبيه الطضليه في المرضى المسنين المصابين باضطراب في وظائف العدة الدرقيظ
151220
(TSH T3, T4)
MMSSP300
SMNC
(EMG)
75258020
75506060
2520