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SREE CHITRA TIRUNAL INSTITUTE FOR MEDICAL SCIENCES AND TECHNOLOGY
THIRUVANANTHAPURAM, KERALA
IS HEARING IMPAIRMENT A NON-MOTOR SYMPTOM IN
PARKINSON’S DISEASE? A PROSPECTIVE OBSERVATIONAL
STUDY
Thesis submitted in partial fulfilment of the rules and regulations for
DM Degree Examination of
Sree Chitra Tirunal Institute for Medical Sciences and Technology
By
DR. KULDEEP SHETTY
DM Neurology Resident
Month and Year of Submission: October 2016
Department of Neurology
Sree Chitra Tirunal Institute for Medical Sciences and Technology
Thiruvananthapuram
2014-2016
DECLARATION
I, Dr. Kuldeep Shetty, hereby declare that this project was undertaken by me under the
supervision of the faculty, Department of Neurology, Sree Chitra Tirunal Institute for
Medical Sciences and Technology.
Thiruvananthapuram Dr. Kuldeep Shetty
Date:
Forwarded
The candidate, Dr Kuldeep Shetty has completed the project under my guidance.
Thiruvananthapuram Dr Asha Kishore
Date Professor of Neurology &
Director of the Institute
SCTIMST, Trivandrum
Forwarded
The candidate, Dr Kuldeep Shetty has completed the project under my guidance.
Thiruvananthapuram Dr Syam K
Date Additional Professor of Neurology
SCTIMST, Trivandrum
Forwarded
The candidate, Dr Kuldeep Shetty has completed the project under my guidance.
Thiruvananthapuram Dr Muralidharan Nair
Date Professor and Head of Neurology
SCTIMST, Trivandrum
ACKNOWLEDGEMENT
I take this opportunity to express my sincere gratitude to Dr.Asha Kishore, Professor of
Neurology and Director, SCTIMST and Dr Syam K, Additional Professor of
Neurology, my guides for the study, for their expert guidance, constant review, kind help
and keen interest at each and every step of the study.
I express my sincere gratitude to Dr. Muralidharan Nair, Professor and Head,
Department of Neurology for his guidance, encouragement and valuable suggestions
during the period of the study.
I am thankful to Mrs Manju Mohan P , Audiologist, Mrs Nandini, Mr Al Ansari and
rest of team of Neurotechnologists for helping me with the technical guidance while
performing the study. I am thankful to Mr Gangadhar Sharma ,psychologist , for his
valuable support coordinating the evaluation of the patients.
I express my sincere thanks to Dr Sankar Sharma Professor of Biostatistics and
Dr. Jissa, Scientist B, Achutha Menon Centre for Health Science Studies for helping me
with the statistical analysis of this study and my colleagues in the Department of
Neurology for their valuable input and assistance to the study. Last but not the least, I
extend my gratitude to all my patients and their primary caregivers and all the healthy
volunteers who willingly participated in this study.
Dr Kuldeep Shetty
Senior Resident
Department of Neurology
Trivandrum, Kerala
CONTENT
Sl.
No. Chapters Page No.
i. Introduction 1
ii. Review of Literature 3
iii. Hypothesis and objectives of the study 13
iv. Subjects and Methods 14
v. Results 17
vi. Discussion 32
vii. Summary and Conclusions 38
viii. References 40
ix. Annexures 44
1
INTRODUCTION
Parkinson disease (PD) is a neurodegenerative disease affecting multiple
systems and clinically characterized by both motor and non-motor symptoms
(NMS).Motor symptoms, being the most conspicuous aspect of PD patients , have
been the subject of clinical research for a very long time. Much of the treatment of PD
including the surgical treatment focus primarily on the motor disabilities.
Simultaneously there has been ever expanding description of non motor
symptoms in PD patients. The non motor symptoms of PD encompass multiple
domains including cognitive, neuropsychiatric, autonomic and sensory symptoms.
The non motor symptoms of PD too significantly contribute towards the morbidity
and the quality of life of the patients. Unlike the motor symptoms which are very
obvious and easily measurable and quantified by clinical examination, the non motor
symptoms are seldom forthcoming . Assessment of non motor symptoms requires a
comprehensive history taking on all the domains of non motor symptoms . Various
scales including NMS Questionnaire , NMSS scale have been developed for a
standardized documentation as well as quantification of non motor symptoms.
Comprehensive care of a PD patient requires adequate addressal of both motor and
nonmotor aspects of the disease.
There have been only few studies assessing the hearing in PD patients. These
studies consisted of assessment of PD patient using Pure Tone Audiometry (PTA)
and brainstem evoked response audiometry ( BERA). The studies on PTA showed
association between hearing loss and PD. But confounding effect of presbycusis was a
limiting factor in these studies. Results of BERA have been variable; few studies
observed prolonged latencies among PD whereas few did not. The aim of this study is
2
to investigate whether hearing loss is truly a nonmotor symptom of PD by recruiting
only early and young onset PD patients and thus overcoming the confounding effect
of presbycusis. . .
3
REVIEW OF LITERATURE
Parkinson’s disease (PD) is a neurodegenerative disease affecting multiple
systems and clinically characterized by both motor and non-motor symptoms
(NMS). The major focus in clinical research in PD had been on the motor symptoms;
however, of late there is an ever increasing evidence that the spectrum of clinical
manifestation of PD is more extensive, also including NMS.
NMS of PD comprised a variety of cognitive, neuropsychiatric, sleep,
autonomic, and sensory dysfunctions.1
The NMS may occur prior to or after the onset of motor symptoms. The
symptoms which usually precede motor symptoms are rapid eye movement sleep
behavior disorder (RBD), constipation, depression and olfactory dysfunction . NMS
are being recognized as an important part of PD symptoms as they amount to
significant disability and affect the quality of life of PD patients.
The assessment of NMS in patients with PD is essential for comprehensive
management. There are specific validated tools available for their assessment. The
non-motor symptoms questionnaire (NMSQ) is a self-administered screening tool
comprising 30 items of NMS. It is a qualitative scale. Quantification of the NMS is
done with the non-motor symptoms scale (NMSS) which is an observer-rated scale .
It has 9 domains consisting of 30 items .
Just as motor symptoms are variably dopa responsive, the NMS too vary in
their response to levodopa. Recent PET studies suggest a dopaminergic contribution
to some NMS and such symptoms related to the dopamine replacement therapy
(DRT).
4
Because levodopa may modify striatal serotonin level , some non-
dopaminergic NMS also respond to DRT. Many other NMS that involve
neurotransmitters other than dopamine, usually do not respond to DRT and need other
treatment.1
Table 1 : Classification of non motor symptoms in PD based on relation to dopamine
replacement therapy:
Non motor
symptom domain
Symptoms
responsive to
Dopamine
replacement
therapy
Symptoms
unresponsive
to dopamine
replacement
therapy
Symptoms
induced by
dopamine
replacement
therapy
Psychiatric
symptoms
Anxiety
Apathy
Anheidonia
Depression
Off period related
panic attacks
Dementia
Confusion
Attention deficit
Cognitive
dysfunction
Delusion
Punding
Impulse control
disorder
Hallucination
Dopa dysregulation
syndrome
Disorders of sleep RBD
Restless leg
syndrome
Periodic limb
movement disoder
Insomnia
Non REM sleep
related disorders
Sleep disordered
breathing
Excessive daytime
sleepiness ( EDS)
Dysautonomic
symptoms
Nocturia
Errectile
dysfunction
Urgency
Sweating
Frequency
Orthostatic
hypotension
GI symptoms Constipation
Dribbling of urine
Unsatisfactory
voiding of bowel
Dysphagia
Aguesia
Reflux vomiting
Fecal incontinence
Diarrhoea
Nausea
Sensory symptoms Fluctuation related
pain
Olfactory
disturbance
Visual dysfunction
Paresthesia
Other symptoms Non motor
fluctuations
Fatigue
Ankle swelling
Blurred vision
5
PD phenosubtype- NMS correlation:
NMS more frequently accompany the non tremor dominant phenotype in
some of the studies . Khoo et al found that sialorrhea was more common, and Muller
et al found constipation , autonomic and sensory symptoms were more common in
PIGD phenotypes. 3,21
Herman et al found that the autonomic symptoms were more
frequent in the PIGD subtypes in the earlier stage of disease.4 Rajput et al studied 166
cases observed a higher cumulative risk of dementia in the PIGD phenotypes .5
Irrespective of stage of disease the non tremor dominant phenotype has been
shown to be more frequently associated with NMS. It has found that there is more
widespread involvement of brain , both the dopaminergic and non dopaminergic
systems and it involves synuclein as well as non synuclein mechanisms.6 Fluctuation
of motor symptoms in PD also has relation to NMS. PD patients with motor
fluctuation were related with more anxiety. The non motor symptoms like anxiety,
depression, fatigue, inner restlessness, pain, concentration/attention and dizziness
tend to fluctuate as well, causing more sensory symptoms in the motor off phase. 1
Hearing loss – Is it another non motor symptom of PD or is it just presbycusis
seen in elderly ?
Presbycusis:
Age related hearing loss in the elderly is termed Presbycusis. Its prevalence in the
general population increases with the age. Multiple risk factors have been found to be
associated with Presbycusis.
6
They are broadly classified into the following categories
1 .Cochlear aging
2 . Environmental factors
3. Medical comorbidities
4 . Genetic factors
Results of animal studies implicate the role of oxidative stress in age related
hearing loss. Cumulating oxidative stress damages the mtDNA in the cochlea causing
apoptosis of cochlear cells. Source of oxidative stress could be general aging process,
exposure to noise, relatively hypoxia involving cochlea as in atherosclerosis,
genetically weak antioxidant defence system Supplementation with antioxidants in
laboratory animals have been shown to slow the AHL progression. 20
Indian normative data on Presbycusis:
The prevalence of presbycusis in the elderly progressively increases with the age.
Presbycusis is likely to start much earlier age, and prevalence goes on increasing with
every decade. There is no normative data on prevalence of age related SNHL in
healthy Indian population below 60 years of age
Table 2. Agewise prevalence of presbycusis in Indian population.19
Age group Prevalence
60-64 50.2%
65-69 55%
70 and above 56.4%
In a study in United States on prevalence of age related hearing loss in the
population between 2001 to 2008 , they observed a steady increase in the prevalence
7
with each decade . It is about 11 percent in ages 44 to 54, 25 percent in ages 55 to 64
and 43 percent in ages 65 to 84.20
.
Figure 1 : Distribution of age related sensorineural hearing loss
As per WHO report , the prevalence of presbycusis is 30-35% in patients of age 60
and above and the prevalence increases to 40-45% in those above 70 years of age.23
Hearing assessment:
A ) Pure tone audiometry :
Perception of pure tones involves the auditory pathway upto primary auditory cortex,
not involving the higher order auditory processing. The pure tone audiometry consists
of the threshold ( y axis) plotted against the stimulating frequency ( x axis) and is
usually measured between 250Hz and 8 kHz.
The stimulating frequency are divided into low , mid and high frequencies.
low frequency – 250 to 1kHz, mid frequency – 2kHz, and high frequency - 4 and 8
kHz. Pure tone threshold calculated by averaging the hearing threshold at 500 Hz,
1kHz and 2kHz is of significant value as it represents the hearing threshold for speech
8
perception. It includes testing of both air conduction ( AC) and bone conduction (
BC) testing and the pattern of curves suggest the type of hearing loss. Sensorineural
hearing loss is associated with AC vs BC gap of < 10dB and conductive hearing loss
is associated with gap of 10 dB.
Most of the SNHL usually affect the higher frequencies more than the lower
frequencies. The classification common used to categorise hearing loss is the
modified Goodman classification.
Table 3: Modified Goodman classification of hearing loss.25
Average hearing threshold level
in dB
Hearing loss grade
Upto 15dB Normal
16- 25 dB Minimal hearing loss
26-40 dB Mild hearing loss
41 – 55dB Moderate hearing loss
56 – 70dB Moderately severe hearing loss
71-90dB Severe hearing loss
>91dB Profound hearing loss
B ) Brainstem evoked response audiometry (BERA):
The BERA is an objective way of eliciting brainstem potentials in response to
audiological click stimuli. There are five well described waves in the auditory evoked
responses ; the corresponding anatomical localization are ; I- spiral ganglion cells of
the cochlea , II – cochlear nucleus cells , III – superior olivary nucleus, IV – lateral
lemnisci, V – inferior colliculi. The BERA parameters used for clinical practice
include latencies of wave I, II, III, IV, V, interpeak latencies( IPLs) I-III, III-V, I-V
9
and also amplitude ratio of V/I . Prolonged wave latencies would help localise the site
of involvement .
Auditory function and Parkinson’s disease:
There have been studies on the auditory function in Parkinson disease patients
the results were variable. There are studies done on audiometry or on BERA in PD
patients.
Studies on BERA date back to 1980s .Gawel et al (1981) demonstrated that
PD patients ( n = 16) had prolonged latency of V as compared to healthy controls ( n
= 16) Limitation of the study was that the controls were not age matched.15
Prasher
et al ( 1986)conducted a 4 armed study comparing BERA in patients with PD ( n =
20 ), MSA ( n = 14) , Pure autonomic failure ( n = 6 ) and controls ( n = 32) . Wave
latencies were found to be significantly prolonged in MSA not in PD or PAF.13
Fradis et al (1988) studied interpeak latencies I-III, III- V, and I-V on BERA was
studied n PD patients with normal audiometry. It was a 3 arm ar study comparing
PD patients on treatment ( n = 17) , PD patients off levodopa for 12 hours ( n = 18)
and controls . All the three interpeak latencies were significantly prolonged (p <
0.02, p < 0.05, p < 0.001 for I-III, III-V, and I-V respectively ) in the levodopa with
held group, without any significant increase in the latencies in PD patients continuing
levodopa as compared to the control group. . Intergroup comparision between treated
PD group versus treatment with-held PD group , revealed significantly prolonged
latency of wave III-V in the latter group. 17
Yylmaz et al (2009)studied 20 patients of PD and 24 age matched controls
were evaluated with audiometry and BERA.PTA revealed statistically significant
increase in the audiometry thresholds at 4 and 8 kHz only as compared to controls.
10
BERA showed wave V latency , and interpeak latency I-V to be
significantly prolonged in PD patients. 16
In another study by Daniel (2013) , BERA
was analysed in PD patients ( n= 34) and age and sex matched healthy controls ( n =
29) which revealed prolonged latencies of II, III, IV, V and III-V interpeak latency .
18 Other studies by Chiappa, Tsuji et al did not reveal evidence of any significant
latency difference in PD patients. Another study by Carmine et al (2012) which had
the largest cohort of PD patients (n = 106) analysed . PTA in PD versus age and sex
matched healthy controls. Study showed statistically significant hearing impairment
in the PD patients and there was significant relation of hearing loss to H and Y staging
, but not to duration of the disease, levodopa equivalent daily dosage, UPDRS score
or side of clinical onset of PD.12
In a study by Ondo et al with questionnaire based assessment of hearing
impairment in geriatric population , Essential tremor patients ( n = 251) had
significantly more hearing impairment as compared to healthy controls( n =127) and
PD patients ( n = 127). 14
11
Table 4 :Summary of studies on PTA or clinical symptoms of hearing loss in PD:
Study
group
Subjects number Investigation
Conclusion
Ondo et al
( 1988)
ET – 250
PD – 127
Control- 127
Questionnaire
based (history)
No significant hearing
impairment in PD as compared
to controls.
Yylmaz et
al (2009)
PD – 20
Controls -24
PTA and BERA Significant hearing impairment
in PD (p < 0.05 for PTA and
BERA)
Carmine et
al (2012)
PD – 106
Controls- 106
PTA Significant hearing impairment
in PD (p< 0.05)
Elderly (p =0.01)and male
( p= 0.006) more prone.
Table 5: BERA based studies in PD patients
Study group Subject number Parameters Conclusion
Gawel (1981) PD – 20
Controls – 24
PTA, BERA Prolonged latency of V in PD
patients ( p < 0.005)
Prasher (1986) PD – 20
MSA – 14
PAF – 6
Controls – 32
BERA No significant difference
compared with healthy controls.
Fradis (1988) PD – 18
treatment
withheld ,17 on
levodopa
Controls – 60
BERA
In PD with withheld Levodopa,
there is prolonged I-III, III-V, I-
V latencies versus controls
Prolonged III-V latencies in PD
with treatment withheld versus
treatment not withheld. .
Yylmaz (2009) PD – 20
Controls -24
PTA, BERA Prolonged latencies of V and I-
V in PD. (p < 0.05)
Daniel ( 2013) PD – 34
Controls – 29
BERA Prolonged latencies of
II,III,IV,V,III-V in PD. (p <
0.05)
12
Both studies on PTA found hearing impairment significantly more common
in PD patients. None of the positive studies too found any correlation between the
duration of the disease and abnormal latencies. All the study had significant number
of elderly patients there was high prevalence of presbycusis in the control group. And
all the studies with hearing impairment in PD patients , the hearing loss was
subclinical.
BERA results across various studies were varying. All the BERA studies
were on small sample size . Only Yylmaz et al studied both BERA and PTA in 20 PD
patients and 24 controls. There has been no study on a purely younger cohort of PD
patients. The limited number of studies on hearing assessment in PD patients
especially with confounding factors of presbycusis , paves the way for further targeted
research into this aspect of non motor symptoms.
13
HYPOTHESIS AND OBJECTIVE OF THE STUDY
Observations from few studies on hearing impairment in PD suggest that it could be
another non motor symptom. We hypothesise hearing impairment to be non motor
symptom of PD. To overcome the confounding effect of presbycusis, subjects
lesser than 55years were chosen for the study as the prevalence of presbycusis is
low below this age.
OBJECTIVES
1. To look for the prevalence of hearing impairment in relatively younger PD
patients (age less than 55 years) as compared to controls and also the pattern
of hearing loss.
2. Comparison of BAEP latencies between PD patients and controls to look for
any difference in wave latencies or interpeak latencies.
3. Association of hearing impairment with other variables among the patients
like other non-motor symptoms, family history, duration of motor
symptoms, stage of PD, fluctuations, dyskinesia, LEDD, UPDRS score. etc.
14
SUBJECTS AND METHODS
Study design:
This study was a hospital based prospective observational study where in the patients
were selected from among the those attending the Movement Disorder clinic and the
controls were the healthy volunteers among general public , hospital fraternity,
visitors .
Study period :
Patients and controls data were included between Dec 2014 to August 2016.
Methodology :
The inclusion and exclusion criteria were as mentioned below.
Inclusion criteria for patients :
1. Diagnosis of Parkinson’s disease by United Kingdom Parkinson Disease Brain
Bank criteria.
2. Age less than 55 years.
Inclusion criteria for controls:
Age and gender matched to patients
Exclusion criteria:
1. Present or past otological diseases; family history of otological disorders
2. Concomitant neurological diseases or other medical diseases known to negatively
affect hearing
15
3 . Patients with marked cognitive impairment and not able to cooperate for
audiometry.
Consecutive PD patients attending the movement disorders clinic who satisfied the
inclusion and exclusion criteria were selected. Evaluation included detailed history ,
NMS questionnaire and clinical examination with UPDRS scores, pure tone
audiometry and BERA. Patients with conductive hearing loss pattern on audiometry
were excluded from the study. 51 consecutive patients PTA were analysed. Age and
sex matched healthy volunteers satisfying the exclusion criteria underwent PTA and
BERA. Cases or controls with conductive pattern of hearing loss pattern on PTA
were excluded from the study .
Ethical considerations:
The study was approved by the Institute Ethical Committee. Written informed consent
was obtained from all the subjects participating in the study. The informed consent
procedure was done according to the guidelines provided in the Declaration of
Helsinki and the ICH E6 Guideline for Good Clinical Practice.
Symptom evaluation :
Detailed neurological history of the PD patients with special focus on the NMS
Questionnaire and the NMS Scale , along with history of any otological l symptoms
or otological disease in past or present. Thorough clinical neurological examination
was done on all the confirmed follow up cases of Parkinson disease patients, UPDRS
score during ON/OFF phase noted , and patients were assigned the H an Y staging
16
after the examination. Basic otological examination was done by the Principal
Investigators.
Audiometric evaluation:
Pure tone audiometry was done for all the selected PD cases and controls and
stimulation was done as per standard protocols – 250Hz, 500Hz, 1kHz, 2kHz, 4kHz
and 8 kHz , both air and bone conduction were recorded in the audiometry lab of our
institute.
BERA:
BERA was performed on all the PD cases and controls in the neurophysiology lab of
our institute. Evoked responses were obtained by stimulating at 60 dB above the
hearing threshold in each ear with masking of the contralateral ear simultaneously
with noise which was 40 dB lower than that in the stimulating ear . The latencies of
wave I, II, III, IV, V and the interpeak latencies I –III, III-V, I-V were recorded in
milliseconds in both the ears. BERA was performed on all the 51 cases of PD and 50
healthy controls.
STATISTICAL ANALYSIS:
The data was analysed using statistics software (SPSS Inc, Illinois,Chicago). The
statistical analysis was done with the help of the Medical Statistics Expert of the
Institute. The descriptive statistics were expressed in means , SD and percentages.
Fisher’s exact test / chi square test were used to compare the prevalence of hearing
impairment between patients and controls and also for investigating for association of
hearing impairment with other categorical variables within the patient and control
groups . The continuous variables were compared using Student’s t test .
17
RESULTS
51 patients of Parkinson’s disease and 50 healthy age and sex matched controls
satisfying the inclusion criteria were included in analysis for the study.
Demographic characteristics:
The mean age of the cases was 44.2years ( ± 6.73 years) and controls was
44.2years ( ± 6.97years)( ( p = 0.96) . Among the cases, 34 were males and 19 were
female. Among controls 33 were males and 17 were females (p =0.83). Among cases
one had diabetes and 3 had hypertension and among controls 2 each had diabetes and
hypertension ( p =0.61 for Diabetes, p= 1.00 for HTN).
The distribution of the age , sex, side of onset of symptoms, H and Y staging,
subtype of PD, UPDRS scores, fluctuations , dyskinesia, family history and LEDD are
tabulated here below.
18
Table 6 : Clinical profile of PD patients:
Variables Distribution
( categorical variables are expressed in number of
patients in each subgroup, continuous variables
expressed in mean with SD and range)
Sex ( M/F) 34/17
Age ( years) 44.2 ± 6.73 years ( range, 28-55 years)
Disease duration ( years)
7.5 ± 5.1 years ( range, 1 -25years).
H and Y stage:
Stage 1
Stage 1.5
Stage 2
Stage 2.5
Stage 3
2
2
17
23
8
Side of onset:
Right sided
Left sided
36
15
Subtype at onset:
Tremor dominant
Rigidity dominant
Indeterminate
16
16
19
Fluctuations (+/-) 31/20
Dyskinesia (+/-) 22/29
UPDRS score ( ON phase) 15.7 ± 8.2 (range , 3 – 36)
Family history (+/-) 8/43
Non motor symptoms (+/-) 43/8
Duration of earliest NMS (
years)
4.2± 3.8 years ( range, 0-20years ).
LEDD ( mg) 645.7 ±312.2mg ( range 0 – 1675mg)
LEDD was calculated using the conversion factors as described here below for all:
19
Table 7. Conversion factors for PD drugs:27
Drug Conversion factor
Immediate Release Levodopa X 1
Controlled release Levodopa X 0.75
Entacapone X 0.33
Pramipexole X 100
Rasagiline X 100
Ropinirole X 20
Amantadine X 1
.
Patients were evaluated for NMS using the NMS questionnaire. The questionnaire
included 30 questions based on the non motor symptoms to be answered as ‘yes ‘or
`no’. Symptoms were further quantified using the NMSS scale based on the severity
of symptoms and their frequency. Non motor symptoms were present in 43 ( 84.3%)
of the PD patients. Mean duration of earliest NMS was 4.2± 3.8 years ( range, 0-
20years). The distribution of the NMS were as described in Table no 8 .
20
Table 8. The distibution of non motor symptoms in PD patients
Non motor symptoms No of pts with the non motor symptom
Hyposmia 6 ( 11.7%)
Constipation 9 ( 17.6)
Urgency 3 (5.8%)
Nonspecific pain 4 (7.8%
Memory loss 1 ( 2%)
Hallucination 1( 2%)
Lack of concentration 1( 2%)
Anxiety 10 (19.6%)
Decreased libido 1( 2%)
Impotence 2 (3.9%)
EDS 5 (9.8%)
Insomnia 7 ( 13.7%)
RBD 15 (29.4%)
Depression 22 (43.1%)
Audiometry:
Hearing loss was classified as per modified Goodman classification. 42 ( 82.4%) of
the 51 PD patients had hearing loss in audiometry, and 22 ( 44%) of the 50 controls
had hearing impairment ( p <0.001). But none of the patients or controls were aware
of their hearing loss.
21
Figure 2. Hearing impairment in cases versus controls :
Hearing loss at lower and higher frequencies
Stimulating frequencies were divided into low (250Hz , 500Hz, 1kHz) , mid ( 2kHz)
and high frequencies ( 4kHz and 8kHz) Comparing the pure tone hearing threshold at
low and mid frequencies , 39 ( 76.5%) of PD patients had hearing loss as compared to
13( 26%) of controls ( p < 0.001). At high frequency, 41 of 51 ( 80.4%) PD patients
had hearing impairment as compared to 22 out of 50 ( 44%) controls ( p< 0.001).
9(17.6%)
28(56%)
42((82.4%)
22(44%)
0
10
20
30
40
50
60
Cases Controls
Nu
mb
er
of
sub
ject
sChart Title
Hearing loss present
normal hearing
22
Figure 3. Distribution of low and mid frequency hearing loss :
12(23.5%)
37(74%)
3976.5%
13(26%)
0
10
20
30
40
50
60
Cases Controls
No
of
sub
ject
s
Chart Title
Low and mid frequency hearing loss
Normal hearing at low frequency
23
Figure 4. Distribution of high frequency hearing loss:
Grade of hearing loss among cases and controls:
Hearing loss was divided into 4 grades as per modified Goodman classification.
Grading of hearing loss was done separately for the two groups;
A ) Low and mid frequency B) High frequency .
At lower and mid frequency, 20 (39%) cases had minimal hearing loss, 19 (37%)had
mild hearing loss, 1 (2%) had moderate hearing loss. Among controls 11 (22%) had
minimal hearing loss, 2 (4%) had mild hearing loss, none had moderate hearing loss.
At high frequency stimulation, among PD patients 9 ( 17.6%) had minimal hearing
loss, 22 (43.1%) had mild hearing loss, 9 ( 17.6%) had moderate hearing loss and 1
had moderately severe and among controls 10 ( 20%) had minimal hearing loss, 8
(16%) had mild hearing loss, 5 (10%) had moderate hearing loss and none had
moderately severe hearing loss .There was statistically significant distribution of
10(19.6%)
28(56%)
41(80.4%)
22 (44%)
0
10
20
30
40
50
60
Cases Controls
Nu
mb
er
of
Sub
ject
sChart Title
High frequency hearing loss
Normal high frequency hearing
24
hearing loss in cases as compared to controls at low and mid frequency stimulation.
There were not enough numbers in each grade to assess statistically significance
among the high grade .
Table 8. Grade of low and mid frequency hearing loss:
Low and mid
frequency Hearing
loss
Cases Controls P ( Fisher exact
test)
Normal hearing 10 ( 19.6%) 27( 54%)
0.002
Minimal 9 ( 17.6%) 10 ( 20%)
mild 22 ( 43.1%) 8( 16 %)
moderate 9 ( 17.6%) 5 ( 10%)
Moderate severe 1( 2%) 1 ( 2 %)
Table 9. Grade of high frequency hearing impairment :
High frequency
Hearing loss
Cases Controls
Normal hearing 11 ( 21%) 37 ( 74%)
Minimal 20 ( 39.2%) 11 ( 22%%)
mild 19 ( 37.3%) 2( 4 %)
moderate 1 ( 4%) 0 ( 0%)
Moderate severe 0 ( 0%) 0 ( 0 %)
Among the cases with hearing impairment , 36 ( 85%) had bilateral hearing loss, 6
( 15%) had unilateral hearing loss and among the controls with hearing impairment,
21 ( 95%) had bilateral hearing loss , 1 ( 5%) had unilateral hearing loss ( p =0.40).
The average threshold ( in decibels) for hearing were tested at 250Hz, 500Hz, 1kHZ,
2kHz , 4 kHz and 8kHz were compared among cases and controls as depicted in the
table below.
25
Table 10. Mean hearing threshold at individual frequencies on PTA:
250Hz 500Hz 1kHz 2kHz 4kHz 8 k Hz
Cases 24.7±7.8 21.5± 6.6 20.0 ± 6.1 19.5 ± 6.9 25.4±10.1 28.6±14.3
Controls 18.5± 6.2 16.1± 6.1 15.0±6.0 14.5± 6.0 20.4± 12.9 18.8± 12.4
p value <0.001 <0.001 <0.001 <0.001 0.03 <0.001
Characteristics of PD patients with hearing loss:
The characteristics of PD patients with hearing impairment were analysed . The
variables included sex , age distribution, H and Y stage, UPDRS scores, side of onset
of PD, duration of illness, fluctuations, dyskinesias, subtype of PD, mean levodopa
equivalent daily dosage ( LEDD), family history of PD, duration of NMS ,
association with various NMS.
Hearing and gender:
Among PD patients 16 females (84.2%) and 26 ( 81.2%) had hearing loss (p =
1.00) Among the controls 17 ( 51%) males and 5 (29.4%) females had hearing loss
(p = 0.22). There was no statistically significant difference across gender in cases
with hearing loss.
Hearing and Age:
Among PD patients, 11 were < 40 year old, 28 were between 40-49 and 12 were
between 50-55yr of age and 8 ( 72%), 23 ( 82%) and 11 ( 91.6% ) of them had
hearing impairment respectively . 2 (16.6%) out of 12 controls aged < 40 years , 10
( 40%) out of 25 controls between 40-49years, 10 (76.9%) out of 13 controls between
50-55years had hearing loss. There was increasing proportion of patients with
hearing loss with increasing age but it was statistically significant only in the controls.
26
Table 11. Age distribution of hearing loss:
Age category Hearing loss in cases
Hearing loss in controls
< 40 years 8 out of 11 (72.7%) 2 out of 12( 16.7%)
40-49years 23 out of 28 (82.1%) 10 out of 25 (40%)
50-55years 11 out of 12 ( 91.7%) 10 out of 13(77%)
p value for
difference in
distribution
0.49 0.009
Apart from this the other observation was that there was a significant trend of
increasing prevalence of hearing loss with age in controls (p = 0.003) but not in cases.
Figure 5.Distribution of hearing loss in age groups among PD patients:
n – number of subjects
n=3(27%) n=5
(17%) n=1(8%)
n=8(73%) n=23
(82%) n=11(92%)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Age < 40years
40-49 years 50-55years
hearing impairment present
normal hearing
27
Figure 6. Age wise distribution of hearing loss in controls:
n = number of subjects
Hearing and H and Y stage:
As per H and Y staging , 2 were in stage 1, 2 in stage 1.5, 17 in stage 2, 23 in stage
2.5 , 8 in stage 3. Among these, 2 out of 2 ( 100%) in stage 1, 0 out of 1 in stage 1.5,
16 out of 17 ( 94%) in stage 2, 17 out of 23 ( 73.9%) in stage 2.5 and 7 out of 8
(87.5%) in stage 3 had hearing impairment. Numbers were too small and therefore
only descriptive analysis was done.
Hearing and UPDRS:
The UPDRS score in On phase were analysed – 47 PD patients had a UPDRS score
available in ON phase. Among the 38 PD patients with hearing impairment the mean
UPDRS score was 15.2±8.2 and among 9 PD patients without hearing impairment,
the mean UPDRS score was 18.4±7.8 (p = 0.29)
n=10(83%)
n=15(60%)
n=3(23%)
n=2
n=10(40%)
n=10(77%)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
<40 years 40-49years 50-55years
hearing impairment present
normal hearing
28
Hearing and side of onset:
Among PD patients, 32 out of 36 ( 88.8%) with onset of symptoms in right sided limb
had hearing impairment and 20 out of 25 ( 80%) with left sided onset of symptoms
had hearing impairment (p= 0.46).
Hearing and mean duration of illness:
The mean duration of illness among the 42 cases with hearing impairment was 7.8
±5.4years and that among the 9 without hearing impairment was 5.9 ±3.4years( p =
0.31)
Hearing and motor fluctuations, dyskinesias:
26 out of 42 ( 61.2%) patients with hearing impairment had motor fluctuations as
compared to 5 ( 55.5%) out of 9 without hearing impairment.( p=0.72).
Dyskinesia were present in 20 out of 42 (47.2%) patients with hearing impairment
and 2 out of 9 (22.2%) patients without hearing impairment (p=0.26).
Hearing and PD subtype:
14 out of 16 (87.5%)tremor onset PD , 11 out of 16 (68.7%) rigidity onset PD and 17
out of 19 ( 89.4%) indeterminate type of onset had hearing impairment (p= 0.22)
Hearing and LEDD score:
Mean LEDD among 42 patients with hearing impairment was 662.7± 320.5mg and
those among 9 without hearing impairment was 566.6mg±272.7mg (p = 0.40)
Hearing and family history :
Family history was positive in 8 out of 42 ( 19%) of PD patients with hearing
impairment and in none out of 9 cases without hearing impairment (p=0.16).
29
Hearing and duration of NMS:
Average duration of NMS was 4.4 ±4.0 years among those with hearing impairment
and it was 3±2.8 years among those without hearing impairment ( p= 0.32).
Table 12 .Clinical profile of PD with hearing impairment:
Variables PD with hearing
impairment
PD without hearing
impairment
P value
Age 45 ± 6.6years 40.8 ±6.5years p = 0.09
Sex :
Male
Female
28/32
16/19
6/32
3/19
p = 1
Duration of illness 7.8±5.4 years 5.9 ± 3.4 years p = 0.31
Side of onset:
Right side
Left side
32/36 ( 88.9%)
10/15 ( 66.7%)
4/36 ( 11.1%)
5/15 ( 33.3%)
p = 0.07
Subtype of PD
Tremor onset
Rigidity onset
Mixed onset
14/16 ( 87.5%)
11/16 (68.8%)
17/19 ( 89.5)
2/16 ( 12.5%)
5/16 ( 31.3%)
2/19 ( 10.5%)
p = 0.22
H and Y stage:
1-2
>2
18/20 (90%)
24/31 (77.4%)
2/20(10%)
7/31 ( 22.6%)
p = 0.25
Fluctuations 26/31 (84%) 5/31 (16%) p = 0 .43
Dyskinesias 20/22 (91%) 2/22 ( 9%) p = 0.13
Family history of
PD
8/8 (19%) 0 (0%) p= 0.16
Mean LEDD 662 ± 320mg 566 ± 272mg p = 0.40
Mean UPDRS
scores
15.1± 8.2 18.4 ± 7.8 p = 0.28
30
Hearing and NMS:
The individual non motor symptoms in the PD cases were analysed with respected to
presence of hearing loss .
Table 13. Profile of non motor symptoms in PD patients with hearing loss:
Non motor symptoms No of pts with the
non motor
symptom
( out of 51 cases )
Patients with
accompanying hearing
loss
p ( Fischer exact
test) - testing
association of
hearing loss with
individual NMS
Hyposmia 6 4 ( 67%) 0.24
Constipation 9 8 (88%) 0.44
Urgency 3 3 ( 100%) 0.44
Nonspecific pain 4 3 (75%) 0.55
Memory loss 1 1 (100%) 0.32
Hallucination 1 1 (100%) 0.84
Lack of concentration 1 1 (100%) 0.82
Anxiety 10 8 (80%) 0.57
Decreased libido 1 1 (100%) 0.82
Impotence 2 0 ( 0%) 0.02
EDS 5 4 (80%) 0.64
Insomnia 7 6 ( 85%) 0.64
RBD 15 14 (93%) 0.16
Depression 22 19 (86%) 0.39
BAEP findings:
BAEP were recorded in 51 PD patients and 50 controls . Taking the standard cut off
for BERA latencies, there was abnormal latencies in two cases and two controls .
Among the cases one had prolongation of latencies of wave IV bilaterally, wave V in
31
right ear, and prolonged interpeak latencies I-III, I- V in the right ear. The other case
had prolonged latencies of wave III, IV and V in the left ear .
Among the controls one subject had prolonged latencies of III, IV , V in left ear, and
the other subject had prolonged latencies of wave V and prolonged interpeak latencies
III-V, I –V in the left ear. Both the cases and controls with abnormal latencies had
sensorineural hearing impairment .
Table 14. The mean latencies of individual waves and interpeak latencies are as
described in the table below:
Wave, interpeak
interval.
Average Latency
In cases
Average latency
among controls p value
I 1.63 ± .12 1.61 ± .10 0.40
II 2.67± .13 2.64 ± .11 0.34
III 3.69± .15 3.67 ± .13 0.67
IV 4.86± .21 4.8 ± .16 0.94
V 5.66± .22 5.67 ± .21 0.71
I-III 2.05± .14 2.06 ± .12 0.68
III-V 1.96± .15 2.01 ± .21 0.14
I-V 4.00± .20 4.02 ± .28 0.73
There was no significant difference in the individual wave latencies or interpeak
latencies between the cases and the controls.
32
DISCUSSION
Auditory function has been studied by a few groups in PD patients in the past
3 decades and the results have been inconclusive. There have been studies with
questionnaires alone, PTA, BERA and combinations as well.
Ondo et al conducted a study based on 10 point questionnaire ( Nursing
home hearing Index questionnaire) on symptoms of hearing impairment and
compared essential tremor patients versus Parkinson disease patients and healthy
controls . No significant hearing impairment symptoms was found among PD
patients and controls , and ET patients had significant hearing impairment. Carmine et
al noted that none of the PD patients in the study who had hearing impairment on
PTA complained of hearing loss. Both Carmine et al and Yylmaz et al used cut off of
26dB to define hearing loss.
Yylmaz et al studied 20 PD patients and 24 healthy controls. PTA and BERA
was done in all, hearing impairment was significantly more common in PD patients.
Carmine et al studies PTA in 106 PD patients and 106 age and sex matched controls
and found that hearing impairment was significantly more common with PD patients.
In the current study , the hearing impairment was classified as per modified
Goodman criteria where in the cut off is 16 dB, as it helps recognise minimal hearing
loss as well. The results showed significantly more hearing impairment among
controls as compared to patients. As the previous two studies on PTA used cut off
for hearing impairment as 26dB, we analysed the data taking 26dB cut off as well.
We observed that hearing impairment was more common in the PD patients at cut
33
off 26dB as well. The controls with hearing loss showed a significantly increasing
proportion of hearing loss across the three age groups while it was not there in the
cases . This suggests that the underlying pathophysiology of hearing loss in the cases
and controls is different supporting the hypothesis of the study. Previous study by
Yylmaz and Carmine et al showed statistically significant high frequency hearing loss
, not at lower frequencies. Majority of patients in previous studies had mild to
moderate high hearing loss. In Carmine et al study 26% had mild (26-40dB) , 63%
had moderate ( 41-70dB) and 11% had severe hearing loss (>70dB) .
In the current study there were no PD patients who complained of any
auditory symptoms . To avoid significant confounding by presbycusis we selected
patients less than 55 years of age as compared to the above mentioned studies which
included elderly patients as well.
Our study showed that both at high as well as low frequencies the hearing
impairment was more common among the PD patients. We analysed hearing
threshold at individual stimulating frequencies and found that it is statistically
significantly higher among cases at each of 250Hz, 500Hz, 1kHz, 2kHz, 4kHz and
8kHz . In degenerative SNHL the higher frequencies are the earliest to be affected.
Subsequently there is affection of all the frequencies.. The involvement of lower
frequencies as well may suggest a more diffuse involvement of the cochlea. In our
study 68% had mild, and 31% had moderate hearing loss , none had severe hearing
loss. As emphasised earlier the lower age cut off could probably account for the
difference in proportions in our study.
34
Clinical profile of PD patients with hearing impairment:
Carmine et al observed that in PD patients, hearing impairment was more
common in the elderly and in males . It was noted that PD patients with hearing
impairment were of higher H and Y stage . There was no effect of duration of the
disease, LEDD, UPDRS score , side of onset of PD.
Apart from the above mentioned patient variables, we also studied other
patient variable viz. subtype of PD at onset, family history of PD, other presence of
other non motor symptoms . No association between any of the these patient profiles
on the presence of hearing impairment. In our study all the patients with family
history ( n=8) of PD had hearing impairment , though there was not enough numbers
to prove clinical association .There was no significant association with any other non
motor symptoms with hearing impairment.
BERA:
The results of BERA in PD patients have been varying across various studies.
One of the earliest studies by Gawel et al observed significantly prolonged latency of
wave V ( p < 0.005) ( PD n = 47, control n = 26) but age of controls were not
specified. Fradis et al showed prolonged III-V interpeak latency in cases while on
temporary levodopa withdrawal .17
But Yylmaz et al showed significantly prolonged
latencies of wave V and I-V interpeak latency (p < 0.05).12
Our study did not show any significantly prolonged latencies or interpeak
latencies across cases and control. There was no association between hearing
impairment with latencies, These findings suggests that the auditory pathway in the
brainstem in PD patients is relatively intact.
35
Table 4 : Summary of studies on Hearing/PTA in PD patients.
Study
group
Subjects number Parameter Conclusion
Ondo et al
( 1988)
ET – 250
PD – 127
Control- 127
Questionnaire
based ( history)
No significant hearing
impairment in PD as compared
to controls.
Yylmaz et
al (2009)
PD – 20
Controls -24
PTA and BERA Significant hearing impairment
in PD
Carmine et
al ( 2013)
PD –106
Controls-106
PTA Significant hearing impairment
in PD
Elderly and male more prone.
Table 5: BERA based studies in PD patients
Study group Subject number Parameters Conclusion
Gawel (1981) PD – 20
Controls – 24
PTA, BERA Prolonged latency of V
Prasher (1986) PD – 20
MSA – 14
PAF – 6
Controls – 32
BERA No significant difference
compared with healthy controls.
Fradis (1988) PD – 18
treatment
withheld and 17
on levodopa
Controls – 60
BERA
In PD with withheld Levodopa,
there is prolonged I-III, III-V, I-
V latencies versus controls
and prolonged III-V latencies vs
PD on treatment.
Ylmaz (2009) PD – 20
Controls -24
PTA, BERA Prolonged latencies of V and I-
V in PD.
Daniel ( 2013) PD – 34
Controls - 29
BERA Prolonged latencies of
II,III,IV,V,III-V in PD.
36
Hypothesis for mechanism of hearing impairment:
The localisation of site of auditory impairment in PD cases is debatable. Alpha
synuclein has been demonstrated in the inner ear and the alpha synuclein dysfunction
could which could possibly explain a peripheral mechanism of hearing loss.28,29
Studies showing prolonged peak latencies postulated that there the involvement of the
central auditory pathways. There are studies of brain perfusion SPECT and fMRI
showing basal ganglia involvement on auditory stimulation. Output from basal
ganglia are directed to the inferior colliculus, medial geniculate nucleus, temporal
cortex. 30-33
Our study, showed abnormality only in PTA with no significant abnormality
in latencies on BERA, emphasising that most likely mechanism is a peripheral
degenerative process.
Strengths of the study:
This is the first study on hearing impairment in exclusively young and early onset PD
thereby significantly overcoming the confounding effect of presbycusis.
Limitations of the study :.
As this was a cross sectional study, temporal evolution of the hearing impairment is
not known. A prospective follow up study may throw light on the temporal evolution
of the hearing impairment, pattern, severity, point at which it becomes clinically
symptomatic.
37
The audiometric evaluation in our study was restricted to PTA and BERA. Auditory
pathway beyond the inferior colliculus is not well represented . Use of additional tests
like otoacoustic emissions could help in more accurate localisation of site of
pathology.
38
SUMMARY AND CONCLUSION
Hearing impairment is an under-recognised non motor manifestation in
Parkinson’s disease (PD). There are only two previous studies on hearing impairment
in PD These studies reported a frequency of SNHL upto 71 % in PD, but failed to
account for presbycusis which is common in the elderly. The current study aimed to
investigate the association of hearing impairment with PD, eliminating the potential
confounders like presbycusis. We conducted a prospective, observational study
including PD patients less than 55 years of age (n=51) and age, gender matched
healthy volunteers (n=50). PD was diagnosed according to the UKPDS Brain Bank
criteria. All subjects underwent detailed clinical examination, puretone audiometry
( PTA) and Brainstem evoked response audiometry (BERA). Hearing impairment
was defined as hearing threshold ≥ 16dB on PTA.
On PTA, higher proportion of PD patients had hearing impairment (82.4% of
cases compared to 44% of controls , p <0.001). Hearing loss among the cases was
significantly higher across both higher (≥ 4kHz ) frequencies ( 80.4% in cases , versus
44% in controls, p < 0.001) and lower ( <4kHz) frequencies (76.5% of cases
versus 26% of controls, p < 0.001) . The BERA was abnormal only in a minority of
patients ( 3.9%) and controls (4%) . There was no significant association of hearing
impairment with sex, duration of illness, H and Y stage, motor fluctuations, PD
subtype, levodopa equivalent daily dosage ,mean Unified Parkinson Disease Rating
Scale scores, other non motor symptoms. SNHL was present in all patients with
familial PD, though the sample size was too small to detect a statistically significant
association.
39
In this group of relatively young onset PD patients, asymptomatic SNHL was a
common non motor manifestation. Considering the normal BERA, the mechanism of
hearing impairment is likely to be peripheral. The strengths of our study include the
recruitment criteria, including exclusively early and young onset PD patients, thus
avoiding the confounding effect of presbycusis. The limitation was that auditory
evaluation was restricted only to PTA and BERA. Further research into the
pathophysiological mechanisms of hearing loss, both peripheral and central, and
longitudinal follow up studies to document its natural progression are warranted.
40
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44
ANNEXURE
LIST OF ABBREVIATIONS
AC Air conduction
BC Bone conduction
BERA Brainstem evoked auditory response
DM Diabetes mellitus
DRT Dopamine Replacement Therapy
EDS Excessive Daytime Sleepiness
ET Essential tremors
fMRI function magnetic resonance imaging
HTN Hypertension
H & Y Hoehn and Yahr
Hz Hertz
kHz Kilo Hertz
IPL Interpeak latencies
45
LEDD Levodopa equivalent daily dosage
MSA Multiple System Atrophy
NMS Non motor symptoms
NMSQ NMS questionnaire
PD Parkinson’s disease
PIGD Postural instability gait disorder
PLM Periodic limb movements
PTA Pure tone audiometry
RBD Rapid eyeball movement sleep behavioural disorder
RLS Restless Leg Syndrome
SNHL Sensory neural hearing loss
SPECT single photo emission computed tomography
UPDRS Unified Parkinson’s Disease Rating Scale
WHO World Health Organisation
46
PROFORMA- PATIENTS
1. Name
2. Age
3. Gender
4. Hospital number
5. HISTORY
a) Duration of motor symptoms:
b) Side of onset:
c) First symptom:
d) Subsequent symptoms:
6. Details of ongoing treatment:
EXAMINATION:
Neurological examination:
Hoehn and Yahr stage:
BAEP Results:
Audiometry Report:
NMS Quest (Attached separately):
NMSS (Attached separately
47
PROFORMA- HEALTHY CONTROLS
1. Name
2. Age
3. Gender
4. Any relevant medical history
EXAMINATION
Neurological examination:
BAEP Results:
Audiometry Report:
NMS Quest (Attached separately):
NMSS (Attached separately)
48
NMS Questionnaire
1. Dribbling of saliva during daytime
2. Loss of change in ability to taste or
smell
3. Difficulty swallowing food or drink or
problems with choking
4. Vomiting or nausea
5. Constipation ( less than three bowel
movements a week ) or having to
strain to pass a stool
6. Faecal incontinence
7. Feeling that your bowel emptying is
incomplete after having been to the
toilet
8. A sense of urgency to pass urine
makes you rush to the toilet
9. Getting up regularly at night to pass
urine
10. Unexplained pains ( not due to known
conditions such as arthritis)
11. Unexplained change in weight ( not
due to change in diet)
12. Problems remembering things that
have happened recently or forgetting
to do things
13. Loss of interest in what is happening
around you or in doing things
14. Seeing or hearing things that you
know or are told are not there
.
15. Difficulty concentrating or staying
focused
16. Feeling sad , low or blue
17. Feeling anxious, frightened or panicky
18. Feeling less interested in sex or more
interested in sex
19. Finding it difficult to have sex when
you try
20. Feeing light headed , dizzy or weak
standing from sitting or lying
21. Falling
22. Finding it difficult to stay awake
during activities such as working ,
driving or eating
23. Difficulty getting to sleep at night or
staying asleep at night
24. Intense, vivid or frightening dreams
25. Talking or moving about in your
sleep, as if your are acting out a dream
26. Unpleasant sensations in your legs at
night or while resting and a feeling
that you need to move
27. Swelling of the legs
28. Excessive sweating
29. Double vision
30. Believing things are happening to you
that other people say are not
49
NON MOTOR SYMPTOM SCALE FOR PARKINSON DISEASE
Symptoms assessed over the last month. Each symptom scored with respect to:
Severity: 0- None, 1- Mild; symptoms present but causes little distress or disturbance to
patient; 2- Moderate: some distress or disturbances to patient; 3 – Severe ; major source of
distress or disturbance to patient.
Frequency: 1 = Rarely ( < 1 /wk) ; 2= Often ( 1/wk); 3= Frequent ( several times per week) ;
4= Very Frequent ( daily or all the time)
Domains will be weighed differentially. Yes/No answers are not included in final frequency x
severity calculation.
Domain 1: Cardiovascular including falls
Severity Frequency Severity X
Frequency
1. Does the patient experience light headedness,
dizziness, weakness on standing from sitting or
lying position ?
2. Does the patient fall because of fainting or blacking
out?
SCORE:
Domain 2: Sleep /Fatigue
3. Does the patient doze off or fall asleep unintentionally
During daytime activites?
( For example, during conversation, during mealtimes, or
While watching television or reading )
4. Does fatigue ( tiredness) or lack of energy ( not slowness)
limit the patient’s daytime activities?
5. Does the patient have difficulties falling or staying asleep?
6. Does the patient experience an urge to move the legs or
restlessness in legs that improves with movement when
he/she is sitting or lying down inactive?
SCORE:
Domain 3: Mood/ Cognition
50
7. Has the patient lost interest in his/her surroundings?
8. Has the patient lost interest in doing things or lack
motivation to start new activities?
9. Does the patient feel nervous, worried or frightened
no apparent reason?
10. Does the patient seem sad or depressed or has he/she
reported such feelings ?
11. Does the patient have flat moods without the normal
“highs” and “lows” ?
12. Does the patient have difficulty in experiencing
Pleasure from their usual activities or report that they
lack pleasure?
SCORE:
Domain 4: Perceptual problems/hallucination
13. Does the patient indicate that he/she sees things
that are not there?
14. Does the patient have beliefs that you know are not
true? ( For example, about being harmed, being
robbed or being unfaithful)
15. Does the patient experience double vision?
SCORE:
Domain 5: Attention/ Memory
16. Does the patient have problems sustaining
concentration during activities?
( For example , reading or having a conversation)
17. Does the patient foget things that he /she has been
told a short time ago or events that happened
In the last few days?
18. Does the patient forget to do things?
SCORE:
Domain 6: Gastrointestinal tract
19. Does the patient dribble saliva during the day?
20. Does the patient have difficulty swallowing ?
21. Does the patient suffer from constipation?
SCORE:
51
Domain 7: Urinary
22. Does the patient have difficulty
Holding urine ?
23. Does the patient have to void
Within 2 hours of last voiding?
24. Does the patient have to get up
Regularly at night to pass urine?
SCORE:
Domain 8: Sexual Function
25. Does the patient have altered
Interest in sex?
26. Does the patient have problems
sex?
SCORE
Domain 9 : Miscellaneous
27. Does the patient suffer from pain
not explained by other known condition?
28. Does the patient report a change in ability
to taste or smell ?
29. Does the patient report a recent change in
weight?
30. Does the patient experience excessive
sweating?
SCORE
TOTAL SCORE:
