Cognitive and Neuromuscular Assessment in Geriatric ... · Cognitive and Neuromuscular Assessment in Geriatric Patients with Thyroid Dysfunction Hala S Sweed1, Azza A Nasser2, Salma

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

Egypt J. Neurol. Psychiat. Neurosurg. Vol. 44 (1) - Jan 2007

236

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-

Hala Sweed et al.

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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.

239

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).


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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


240

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

Hala Sweed et al.

241

Sural Value 6.90 ± 2.13 5.10 ± 0.95


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


Rt Med Value 4.50±0.82 2.80±0.25


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,


242

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.

Hala Sweed et al.

243

Fig. (3): Shows increased duration and average amplitude of motor unit

potential (neurogenic pattern) with polyphasia.


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.


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.


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.

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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

Documents

Cognitive and Neuromuscular Assessment in Geriatric ... · Cognitive and Neuromuscular Assessment in Geriatric Patients with Thyroid Dysfunction Hala S Sweed1, Azza A Nasser2, Salma