Poster session 12: Neuropathy

Poster session 12: Neuropathy
P12.01
Development of the local made disposable 10-gram Semmes-Weinstein monofilament
in Thailand
Pasu Sirisalee, National Metal and Materials Technology Center, Pathumthani, Thailand
Danu Prommin, National Metal and Materials Technology Center, Pathumthani, Thailand
Gulapar Srisawasdi, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand
Navaporn Chadchavalpanichaya, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand
Atchara Suwannakin, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand
Aims: The 10-gram Semmes-Weinstein monofilament has been accepted as a standard tool
to identify loss of protective sensation in the feet of diabetic patients. It is also recommended
in the Thai clinical practice guideline for prevention and management of diabetic foot
complications. However the monofilament is not widely available in Thailand. The imported
monofilaments are considerable expensive. The aim of this study is to find a technique to
make a disposable monofilament that is accurate and affordable for Thailand context.
Methods: Review of literatures showed no published specifications of the monofilament. The
investigators set the concepts that materials must be locally available. Also the unit cost
must be affordable for primary care units in Thailand. The nylon monofilaments with different
diameters were tested with a testing apparatus which specially developed for testing the
monofilament’s force. Monofilament’s fabrication technique was developed and the accuracy
test of monofilament force was performed.,
Results: The specification of local made disposable 10-gram Semmes-Weinstein
monofilament was identified. The material used is available in Thai market. The force of the
monofilaments developed was in an acceptable range for a standard clinical practice. The
investigators decided to use a monofilament as a disposable one to ensure its hygiene and
accuracy. The unit cost of the monofilament is expected to be less than 1 US Dollar.
Conclusions: The local made disposable 10-gram Semmes-Weinstein monofilament was
developed. The material is easily available and affordable for Thailand context. The
accuracy of the monofilament’s force is measured by a dedicated testing apparatus.,
Availability, durability, and cost are important issues to be concerned for medical tools that
have been recommended to use worldwide. The result from this study could be applied to
other countries that are in similar conditions as Thailand.
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Page 1 of 9
P12.02
A statistical approach to identify the contribution of clinical variables to diabetic
neuropathy classification
Cristina Sartor, University of Sao Paulo, Sao Paulo, Brazil
Eneida Suda, University of Sao Paulo, Sao Paulo, Brazil
Vincent Vigneron, University of Evry Val D’essonne, Evry, France
Isabel Sacco, University of Sao Paulo, Sao Paulo, Brazil
Aims: To identify which are the most important DPN-related variables that can discriminate
between groups of patients with diabetic polyneuropathy (DPN) that could represent a
progressive worsening of the disease before the onset of plantar ulceration or amputation.
Methods: We analyzed 193 diabetic patients. A total of 16 DPN-related variables of signs,
symptoms and foot inspection characteristics were assessed, based on the literature and
Consensus on Diabetic Foot [1 2]. We used multiple correspondence analysis and Kohonen
algorithm [3] to group the variables into micro and macro-classes (groups) and to identify
clusters of patients that represent different conditions of the DPN.
Results: Four distinct groups were observed. It was possible to identify a group without any
indication of DPN installation. The remaining groups indicate a progressive loss of the
vibration perception, without a worsening of symptoms or tactile perception. The two
intermediate groups are represented by different aspects of DPN: one is mostly composed
by the DPN symptoms, and the other is composed by the incipient vibration impairment,
callus and crack formation and foot arch alteration. The fourth group indicated a more severe
feet and DPN condition, including ulceration and amputation, absence of vibration and tactile
perception (irrespective how many compromised foot areas) and worse feet deformities and
cracks/callus formation.
Conclusion: Vibration perception was more informative than tactile sensitivity in
discriminating the early DPN onset since its impairment is evident in more groups. The
symptoms, callus and cracks do not discriminate the severity status, and should be
interpreted in association with other clinical variables. There is a need for reconsideration of
the current screening techniques to clinically determine the early onset of the neuropathy
using the tactile perception.
Acknowledgments: FAPESP (2011/19304-4), CNPq (151531/2013-7) and Catedras
Francesas no Estado São Paulo.
References:
[1] Bakker K;Diab Metab Res Rev; 28 Suppl 1: 225-231;2011
[2] Perkins BA;Diab Care 24: 250-256;2001
[3] Andersen EB;Springer 1989.
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Page 2 of 9
P12.03
Vibration and Monofilaments testing to identify high risk patients. Is it enouph?
Christos Manes, Diabetes Center General Hospital Papageorgiou, Thessaloniki, Greece
Christos Mellidis, Diabetes Center General Hospital Papageorgiou, Thessaloniki, Greece
Michael Psallas, Diabetes Center General Hospital Papageorgiou, Thessaloniki, Greece
John Sapakos, Diabetes Center General Hospital Papageorgiou, Thessaloniki, Greece
John Tsavdaridis, Diabetes Center General Hospital Papageorgiou, Thessaloniki, Greece
Theodoros Rogkotis, Diabetes Center General Hospital Papageorgiou, Thessaloniki, Greece
John Koukoutsis, Diabetes Center General Hospital Papageorgiou, Thessaloniki, Greece
George Ziotas, Diabetes Center General Hospital Papageorgiou, Thessaloniki, Greece
Peripheral neuropathy increases the risk of foot ulceration and contributes to lower extremity
amputations in diabetic patients. Vibration Perception Tests and Semmes Weinstein
Monofilaments (testing large fiber dysfunction) are advocated in guidelines to identify
neuropathic patients. Small fiber testing is not recommended as a screening tool.
Aim: To investigate the predominant type of nerve fiber dysfunction in diabetic patients in
relation to diabetes duration, age, sex and type of diabetes.
Patients and Methods: 410 diabetic patients included. Males were 186 (45.4%) and 370
(91%) type 2 diabetics. Mean age and diabetes duration were 65.67±11.65yrs and 14.71±
10.47yrs respectively. The Neuropathy Disability Score (NDS) was used to quantify clinically
the overall nerve dysfunction. A NDS≥5 considered abnormal for overall nerve function and
NDS1≥2 for small fiber dysfunction -SFD- and NDS2≥2 for large fiber dysfunction -LFD- were
considered abnormal too. The duration of Diabetes was divided in 4 stages: 0-5, 6-10, 11-15
and >16. Age and sex were recorded too.
Results: 1) Neuropathy was diagnosed in 179 patients (43.7%) (Group A) whereas in the
remaining population were 231 patients (56.3%) (Group B). 2) 26.8% of the patients
expressed SFD and 14.1% LFD (p<0.001), 3) SFD was more frequent in all stages of
diabetes duration than the LFD (p<0.05). 4) Odds ratios for SFD vs LFD were higher in all
the duration stages 5) In multivariate analysis age, duration of diabetes, sex but not Type of
Diabetes were significant factors affecting nerve damage (small and large fibers). 6) Testing
for only LFD did not identify substantial percentages of those with SFD as at risk patients
(10%, 44%, 43% and 25%) for all the stages of Diabetes duration.
Conclusion: Careful physical examination is more useful in identifying patients at risk for FU,
since using Vibration and Monofilaments testing alone can not identify all the patients at risk
for FU and amputations.
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Page 3 of 9
P12.05
The effects of random vibrations on the vibratory perception threshold of the foot and
standing balance in people with diabetic neuropathy
Jennefer Zwaferink, Ziekenhuisgroep Almelo, Almelo, Netherlands
Background: People with diabetes mellitus often suffer from polyneuropathy. Reduced
somatosensation of the feet due to polyneuropathy is one of the major risk factors for
ulceration at the plantar side of the feet and may often cause problems in balance. It has
been shown that the application of a mechanical noise signal to the feet can reduce the
sensation threshold and improve standing balance.
Aim: To investigate the effects of new vibrating insoles on vibration perception threshold
(VPT) and balance of people with diabetic neuropathy with and without a history of
ulceration.
Methods: Patients with diabetic neuropathy without a history of ulceration and patients with
diabetic neuropathy with a history of ulceration at metatarsalphalangeal, (MPT), hallux or
heel region were included. VPT of all included patients was between 25 and 45 Volts. VPT
was measured at four locations of the plantar side of the foot using a biothesiometer when
patients were lying prone with an actuator placed against the plantar side of the foot.,
Balance was measured when patients were standing on a force platform while wearing
standardized shoes in which vibrating insoles were placed. Both measurements were carried
out when the insoles were either turned on (i.e. random vibrations applied) or off (i.e. no
random vibrations applied).
Results: Since the inclusion is still going, only preliminary results can be described.
Preliminary results show an improvement in balance when a mechanical noise signal was
applied to the plantar side of the feet. When the attention of the patients was distracted with
the aid of an attention-demanding task, balance was improved more. The results also show
a reduction in sensation threshold when a random vibration was applied to the feet by
means of an actuator.
Conclusions: Preliminary results indicate the possibility that a mechanical noise signal can
have a beneficial effect on balance and VPT in patients with diabetic neuropathy. Until the
end of the study (April 2015), no conclusions can be drawn.
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Page 4 of 9
P12.06
Utility of E-Med scan and foot mate print technologies and to correlate it to diabetic
neuropathy, Dar es Salaam, Tanzania
Zulfiqarali Abbas, MUHAS / AMC, Dar es Salaam, Tanzania
Janet Lutale, MUHAS, Dar es Salaam, Tanzania
Lennox Archibald, University of Florida, Gainesville, United States
Background and aims: In Africa, diabetic foot ulceration is often associated with peripheral
neuropathy (PN) and substantial morbidity and mortality. Thus new affordable technologies
for PN screening to improve patient outcomes are needed. We carried out this study to (i)
evaluate two technologies the foot E-med scan system (EMS) and the simple Foot Mate
print (FMP) in plantar pressure measurement; and (ii) correlate these measurements with
PN ascertained clinically.
Materials and methods: During January 2011 – October 2014 (study period), all patients
attending a diabetes centre in Dar es Salaam, Tanzania, were evaluated clinically. Pressure
at various sites on each foot was measured with EMS technology and FMP with an ink pad
(dark areas reflected high pressures.) PN was ascertained at standard anatomic sites with a
thermal sensation machine for pain (warm, heat, cold), monofilament for protective
sensation, and biothesiometer for vibration.
Results: Of 2 154 patients enrolled during the study period, 1 237 (57%) were male and 1
154 (53%) had PN by clinical assessment. Median age =52 (range: 11-90) years; median
body mass index=29 (range: 14-59) kg/sq m). Patients with PN were significantly more likely
than those without PN to be older (54 vs. 50 years, p <0.01) or to have a longer diabetes
duration (6 vs. 4 years, p <0.001). In addition, per EMS technology, patients with PN were
more likely to have significantly higher plantar pressures at the big toe (p <0.0001), 3rd, 4th,
and 5th toes (p <0.0001), central hind foot (p <0.05), and mid hind foot (p=0.005) versus
patients without PN. In contrast, FMP recorded high plantar pressures for PN patients only at
the 2nd (p <0.05) and 3rd (p=0.008) toes.
Conclusion: Pressure measurements were largely predictive of PN. While EMS was more
sensitive than FMP in detecting high plantar pressures in patients with underlying PN
confirmed by thermal sensation, biothesiometry, and monofilament testing across various
anatomic areas of the foot, FMP was sensitive in predicting problems mainly in the toes
rather than the hind foot. Despite these differences, both technologies have key major roles
to play in the management of diabetic foot complications in Africa and other countries with
limited resources.
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Page 5 of 9
P12.07
Effect of a therapeutic stimulation device on postural balance in patients with diabetic
peripheral neuropathy
Gurtej Grewal, Interdisciplinary Consortium no Advanced Motion Performance & Southern
Arizona Limb Salvage Alliance, University of Arizona, Tucson, AZ, United States
Saman Parvaneh, Interdisciplinary Consortium on Advanced Motion Performance &
Southern Arizona Limb Salvage Alliance, Tucson, AZ, United States
Jacqueline Lee-Eng, Interdisciplinary Consortium on Advanced Motion Performance &
Southern Arizona Limb Salvage Alliance, Tucson, AZ, United States
Robert Menzies, Hamad Medical Co. Doha, Doha, Qatar
Talal Talal, Hamad Medical Co. Doha, Doha, Qatar
Lawernce Lavery, University of Texas Southwestern Dallas, Texas, Dallas, United States
David Armstrong, Interdisciplinary Consortium on Advanced Motion Performance & Southern
Arizona Limb Salvage Alliance, Tucson, United States
Bijan Najafi, Interdisciplinary Consortium on Advanced Motion Performance & Southern
Arizona Limb Salvage Alliance, Tucson, AZ, United States
Aim: The purpose of this study was to explore the effect of a therapeutic electrical
stimulation device on postural balance in patients with diabetic peripheral neuropathy (DPN).
Methods: In a double blinded study we recruited a sample of 27 patients with DPN from
outpatient podiatry clinics (Age: 57.8±10.2 years, Body Mass Index (BMI): 30.0±6.1,
Vibration Perception Threshold Score: 34.2±8.5 v, HbA1C: 9.1±2.0). Patients were
randomized to either active group (IG, n=17) or sham group (n=10). Both groups received
identical plantar stimulation devices with electrodes for 6 week use (1 hour a day for each
foot), however the device was set for stimulation only for the active group. Postural balance
was quantified by sway of ankle, hip and center of mass (CoM). Postural assessment were
performed at baseline and every 2 weeks. Independent t-test and repeated measures
ANOVA was used to compare group mean differences with p value set to 0.05 and intentionto-treat analysis.
Results: No difference were observed between the groups for age, BMI, VPT or HbA1c
(p>0.050). Baseline parameters of postural sway were also not significantly different
between the groups (p>0.050). Two participants dropped out from sham group and 3 from
active group. Over the period of 6 weeks of therapy ankle and CoM sway reduced
significantly in active group (p=0.008 and p=0.020 respectively) during eyes open balance
assessment. The reductions at week 2, 4 and 6 were 34.4%, 22.4% and 21.4% for ankle and
29.5%, 23.2% and 30.7% for CoM respectively. Sham group did not have a significant
change with p=0.293 for ankle and p=0.608 for CoM sway parameter. During eyes closed
assessments active group had significant reductions only for ankle sway (p=0.019) with
actual reductions of 28.9%, 33% and 24.8% at week 2, 4 and 6. CoM reductions did not
reach level of significance (p=0.075). No significant reductions were observed for sham
group with p=0.154 for ankle sway and p=0.224 for CoM sway parameter.
Conclusions: The results from this study suggest that significant improvements in postural
sway can be achieved from use of a portable therapeutic device through plantar stimulation
in patients with DPN. Future study with larger sample size should confirm the findings of this
study.
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Page 6 of 9
P12.08
Heart rate response: a complementary measure for fall-risk assessment in patients
with diabetic peripheral neuropathy
Saman Parvaneh, University of Arizona, College of Medicine, Tucson, AZ, United States
Gurtej Grewal, University of Arizona, College of Medicine, Tucson, AZ, United States
Robert Menzies, Hamad Medical Co, Doha, Qatar
Talal Talal, Hamad Medical Co, Doha, Qatar
David Armstrong, University of Arizona, College of Medicine, Tucson, AZ, United States
Martha Mohler, University of Arizona, College of Medicine, Tucson, AZ, United States
Bijan Najafi, University of Arizona, College of Medicine, Tucson, AZ, United States
Nima Toosizadeh, University of Arizona, College of Medicine, Tucson, AZ, United States
Aim: Fall-risk assessment in patients with diabetic peripheral neuropathy (DPN) is vital for
an early intervention and avoiding fall related injuries. Current methods lack physiological
biomarker of fall-risk. This study explored heart rate (HR) response to balance to objectively
assess fall-risk. We hypothesized that maintaining balance during absent of visual feedback
would trigger discernible changes in HR among DPN subjects.,
Methods: 18 people with DPN (Age: 56.8±7.7, 85% male) were recruited and categorized as
“fallers” (n=8) or “non-fallers” (n=10) based on 1 year past history. HR and balance data was
recorded using validated wearable sensors. Baseline HR was recorded while participants
were relaxed sitting. HR response to balance was recorded during eyes-closed Romberg
(ECR) balance test. During the test participants brought their feet together (not touching) and
arms crossed across chest for 30 seconds. Balance was quantified by center of mass (CoM)
area of sway. HR response to balance was assessed by calculating HR average difference
between ECR and baseline divided by the baseline value (ΔHR). ANCOVA test was used to
explore between group differences after adjusting with age and BMI. Binary regression
model was used to evaluate independent predictors. Between group discrimination
sensitivity and specificity were examined by using age and BMI as independent variables
together with CoM sway (Model1), ΔHR (Model2), and combination of CoM Sway and ΔHR
(Model 3).
Results: CoM sway was 3.01±0.83 cm2(125.3%, p= 0.011) higher in fallers compared to
non-fallers. ΔHR was in average 7.1±2.1% (97.2%, p=0.082) higher in fallers compared to
non-fallers. Sensitivity and specificity to discriminate between groups were, respectively
87.5% and 80.0% for the Model1, 75.0% and 90.0% for the Model2, and were enhanced to
100% for the Model 3.
Conclusions: Results demonstrate that HR response to balance could be considered as a
physiological biomarker to assess fall-risk. Furthermore, our results suggest that combining
balance test and heart rate response to balance allows discriminating between fallers and
non-fallers in people with DPN. However, the results need to be confirmed in larger samples
and in prediction of prospective falls.
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Page 7 of 9
P12.09
Are Caveolin-1 and NFD related to Pathophysiological Progression in femoral nerves
of diabetic foot amputation patients with neuropathy?
Ding Min, Tianjin Medical University Metabolic Diseases Hospital, Tianjin, China,
Wang Penghua, Tianjin Medical University Metabolic Diseases Hospital, Tianjin, China,
Jun Xu, Tianjin Medical University, Tianjin, China
Aim: To observe the pathological changes of femoral nerves in diabetic foot amputation
patients with neuropathy, to investigate the factors that impact Caveolin-1 in Schwann cells
of femoral nerve and nerve fiber density(NFD), to explore if Caveolin-1 and NFD related to
the pathophysiological progression.
Method: Thirty-seven diabetic foot amputation patients were consecutively recruited from
inpatients of Tianjin Medical University Metabolic Diseases Hospital between January 2003
and November 2005. Symptoms and signs of neuropathy were observed, Scores of TCSS
were recorded, nerve conduction velocity was tested, HbA1c was measured. Femoral
nerves were obtained in 2-3 minutes after amputation. HE and Masson staining were used
for pathological observation. Immunohistochemistry was used to observe changes of axons
and count NFD.
Results: Pathological changes in femoral nerves were obvious. Linear regression analysis
showed that Caveolin-1 was associated with HbA1c (r = -0.840; P = 0.000), TCSS (r =
0.667; P = 0.000), sensory nerve conduction velocity (r = 0.546; P = 0.000), motor nerve
conduction velocity(r = 0.369; P = 0.024), NFD(r = 0.7149; P = 0.000) and NFD was
associated with HbA1c (r = -0.548; P = 0.000), TCSS (r = 0.667; P = 0.000), respectively.
Stepwise regression models showed that HbA1c and NFD were the independent factors of
caveolin-1(R2=0.787, F=46.073, P = 0.000), Caveolin-1 and course of diabetes were
independent factors of NFD (R2=0.691, F=27.911, P = 0.000).
Conclusions: Caveolin-1 and NFD are related to Pathophysiological Progression in the
femoral nerves of diabetic foot amputation patients with neuropathy.
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Page 8 of 9
P12.10
Decompression of lower extremity nerves followed by topical subepineural VEGF-165
plasmid injection prevents diabetic neuropathy progression
Maciej Zielinski, Poznan University of Medical Sciences, Poznan, Poland
Fryderyk Pukacki, Poznan University of Medical Sciences, Poznan, Poland
Zbigniew Krasinski, Poznan University of Medical Sciences, Poznan, Poland
Marcin Gabriel, Poznan University of Medical Sciences, Poznan, Poland
Lukasz Dzieciuchowicz, Poznan University of Medical Sciences, Poznan, Poland
Ewelina Grabska, Poznan University of Medical Sciences, Poznan, Poland
Artur Druzdz, City Hospital of Poznan, Poznan, Poland
Maciej Malecki, Institute of Cell Biology, Onkology Center of Warsaw, Warsaw, Poland
Grzegorz Oszkinis, Poznan University of Medical Sciences, Poznan, Poland
Aim: Nerve decompression, proposed by AL. Delllon has potential in the treatment of
diabetic neuropathy. However, it is not a standard, due to its questionable efficacy. VEGF
presents agiogenic and neurogenic potential and was showed to improve nerve
regeneration. We analyzed therapeutic effect of lower extremity nerve decompression
followed by topical, VEGF-165 gene therapy in neuropathic diabetic foot prevention.
Method: From 2006 to 20012, 59 diabetic (26W 33M) with entrapment neuropathy
underwent Dellon’s operation. Average age and diabetes duration were 58 4(48-71) and 7
8(5-18) years respectively. Total of 59 lower extremities had triple decompression of tibial,
common peroneal and deep peroneal nerve. This gave in total 177 decompressions.
Patients were randomized into two study groups: Group I(decompression alone), Group
II(decompression followed subepineural injection of VEGF165plasmid). Postoperatively, at
14 days and 1 3 6 and 12 months: healing time and nerve function improvement according
to VAS scale, ENG and PSSD were assessed.
Results: No surgical complications were noticed. Average healing time was 18(7-35)days. 6
8%(4/59) of patients presented significantly longer healing period of the ankle wound.
Subjective patients’ assessment revealed in 64 4%(38/59) of operated limbs significant
symptoms relief, in 23 7%(14/59) medium and insignificant in 11 9%(7/59). These results
were reflected in ENG and PSSD evaluation. Negative correlation between diabetes duration
and, treatment efficacy was detected. None of the operated patients presented increase in
diabetic foot development. Comparison of study groups did not revealed statistical
significance. However the trend, towards longer nerve regeneration effect duration was
noticed among treated with decompression and VEGF.
Conclusion: These results suggest usefulness of lower extremity nerve decompression in
the prevention of naturopathic diabetic foot development. Topical VEGF165 gene therapy
enhance and stabilize therapeutic effect of decompression. Further investigation with a
larger group is needed to define optimal moment of surgical intervention and subepineural
VEGF165 gene therapy for its highest potential efficacy.
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