Diabetic neuropathy taking evidence to clinic

presentation on diabetic neuropathy

1. 1
Diabetic Neuropathy : Taking Evidence
to Clinic
Focus on Triple therapy
Dr Praveen Gupta
Director and head of Neurology
Fortis Institute of Neurosciences Gurgaon

2. 2
What is a neurologist doing here?

3. 3
Indian scenario
According to the Diabetes Atlas
2006, India has the largest number
of diabetic patients in the world:
40.9 million in the year 2007 and
expected to increase to 69.9 million
by the year 2025
Prevalence of diabetes in urban
Indian adults is 12.1%.
Prevalence of neuropathy in South
Indian type 2 diabetic subjects is
19.1%.
Ramachandran A, Snehalatha C, Kapur A, et al. High prevalence of diabetes and impaired glucose tolerance in India. National Urban Diabetes Survey. Diabetologia; 2001.
44 : 1094-101.
Ashok S, Ramu M, Deepa R, Mohan V. J Assoc Physicians India. Prevalence of neuropathy in type 2 diabetic patients attending a diabetes centre in South India; 2002
Apr.50:546-50

4. 4
Incidence of Diabetic Neuropathy
as a proportion of all diabetics 20 years after diagnosis
No neuropathy
10%
Asymptomatic
40%
Symptomatic
50%

5. 5
Pathophysiology
Not fully understood

6. 6
Mechanisms
Polyol pathway
AGEs
Proteinkinase C activation
Hexosamine Pathway
Microangipathy
Immune mechanisms

7. 7
PATHOPHYSIOLOGY OF DIABETIC
NEUROPATHY
FactorsFactors EffectsEffects
Polyol pathwayPolyol pathway
11
•Decreases membrane NaDecreases membrane Na
++
/K/K
++
-ATPase -ATPase
activity, activity,
•Impairs axonal transportImpairs axonal transport
•Structural breakdown of nerves, causing Structural breakdown of nerves, causing
abnormal action potential propagation. abnormal action potential propagation.
Advanced Glycation Advanced Glycation
End products End products
(AGE)(AGE)
22
•Disrupts neuronal integrity and repair Disrupts neuronal integrity and repair
mechanisms through interference with mechanisms through interference with
nerve cell metabolism and axonal transportnerve cell metabolism and axonal transport
Oxidative stressOxidative stress
33
•Direct damage to blood vessels leading to Direct damage to blood vessels leading to
nerve ischemianerve ischemia
•Facilitates AGE reactionsFacilitates AGE reactions
Related contributing Related contributing
factors factors
•Altered gene expression with altered Altered gene expression with altered
cellular phenotypescellular phenotypes
•Reduction in neurotropinsReduction in neurotropins
•Nerve ischemiaNerve ischemia
1. Neurology.
 Aug 11 1999;53(3):580-91
2. J Neurol Sci.
 Mar 1995;129(1):62-8.
3. Diabetes Care.
 Nov 2006;29(11):2365-70.
7
7

8. 8

9. 9

10. 10
Case 1
•Mr RG 65 year male diabetic for 20 years
presented with progressive difficulty in
climbing stairs , pain legs burning since
last two months
•Examination ; Proximal weakness > Distal ,
decreased ankle and knee jerks in legs
weakness in hands mild sensory loss

11. 11
Case 1
•NCV mild decrease in conduction velocity
in all sensory nerves with increased
latencies, motor NCV reduced with
increased latencies report compatible with
diabetic neuropathy
•Diagnosis ? Diabetic Neuropathy

12. 12
•Does everybody agree

13. 13
Case 1
•Management
•Epalrestat
•Alphalipoic acid/Methycobal
•TCA
•Anticonvulsant

14. 14
Case 1
•No improvement
•Now what

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Rethink Diagnosis
•Demyelinating Neuropathy ? CIDP ?
Paraproteinemia . Clue Motor weakness in
upper limbs
•CSF protein raised
•Nerve biopsy : inflammatory demyelinating
neuropathy
•Treated with IVIG better

16. 16
Take Home Message
•All neuropathy in a diabetic is not diabetic
neuropathy .

17. 17
Non- Diabetic Neuropathy in a Diabetic
When to suspect?
1.Rapid development (except acute neuropathy of diabetes)
2.Progression or Evolution inspite of good metabolic control
3.Marked asymmetry of neurological deficits
4.Predominant motor deficits
5.Upper limb involvement
6.Family history of non diabetic neuropathy
7.Presence of other etiological factors:
Alcohol abuse
Malnutrition
Malignancy (paraneoplastic syndrome)
Neurotoxic drugs- Isoniazide
B-12 deficiency
17

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Risk Factors
•Glucose control
•Duration of diabetes
•Damage to blood vessels
•Mechanical injury to nerves
•Autoimmune factors
•Genetic susceptibility
•Lifestyle factors
–Smoking
–Diet
UKPDS

19. 19
Case 2
•Mr GS 55 year male diabetic for 5 years
presented with mild burning in legs , Pins
and needles worse at night asymptomatic in
day
•Examination ; Normal

20. 20
Case 2
•NCV Normal
•Diagnosis ?
•What tests to do

21. 21
Case 2
•Monofilament testing
•Test for small fibre neuropathy like QST

22. 22
Case 2
•Normal
•Now what
•Can it be diabetic neuropathy

23. 23
Case 2
•Yes in small fibre neuropathy sometimes all
test can be normal

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Common DPN : criteria
•Confirmed : Symptoms + Signs + NCS
•Probable : Symptoms +signs NCS normal
•Possible : either symptoms or signs
•Subclinical : No symptoms/ signs NCS abn.

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However Rethink Diagnosis
•It could be B 12 deficiency neuropathy very
common in India
•It could be restless legs syndrome, which
won’t respond to pain medication, but
responds to dopamine agonists

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Take Home Message
•If in doubt keep differential diagnosis open

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Case 3
•Mr RR 50 year male diabetic for 5 years
presented with mild burning in hands , Pins
and needles worse at night asymptomatic in
day
•Examination ; Normal

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Case 3
•Now what
•Can it be diabetic neuropathy
• What Tests

29. 29
Case3
•NCV shows demylination in legs and in
some nerves in hands.
•Imp: ? Diabetic neuropathy
•Do you agree .

30. 30
Case 3
•Diagnosis CTS present in 30% diabetics
•Most common mononeuropathy in diabetes
•Clue : Median nerve involved Ulnar nerve
spared .
•Others common mononeuropathies : Ulnar ,
peroneal.
•Treatment : CTS splint,I/a injection, surgery .

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Take Home Message
•NCV reporting if done without following
clinical status can be misleading in
impression.

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Case 4
•Mr TN 52 year male diabetic for 5 years
presented with mild burning in legs , Pins
and needles worse in day increases as he
walks
•Examination ; Normal

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Case 4
•NCV Normal
•Diagnosis ?
•What tests to do

34. 34
Case 4
•Monofilament testing

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Case 4
•Abnormal

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Case 4
•Now what
•So this is diabetic neuropathy ?

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However Rethink Diagnosis
•Examine pulses in legs when there is pain
in legs
•It may be peripheral vascular disease
•It may be lumber canal stenosis SLR and
clinical examination is normal in LCS

38. 38
Case 5
•MR JR 60 year male diabetic for 20 years
presented with progressive difficulty in
walking with severe pain in right leg
inability to lift foot , pain legs burning
since last two months
•Examination ; wasting of tibilis anterior
mild wasting of gastronemius , decreased
ankle jerks no sensory loss

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Case 5
•NCV asymmetrical involvement of rt CP
and tibial nerves . Mild decrease in
conduction velocity in all sensory nerves
EMG neurogenic .
•Diagnosis ? Largely motor asymmetrical
subacute neuropathy with wasting

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Case 5
•Imp: Diabetic amyotrophy

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Case 5
•Not really
•PIVD with lumber radiculopathy
•Why

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Compare
•Diabetic amyotrophy
•Proximal
•Affects quadriceps
•Distal nerves may be
normal
•Weight loss
•Spontaneous improvement
•Pain dose not change on
walking
•PIVD
•Usually distal
•Affects TA, EHL
•Sensory nerves spared
• pain may be worse on
walking

43. 43
Case 6
•MR as 36 year male diabetic for 15 years
presented with diplopia gradually
progressive
•Examination ; inability to move right eye
inward, pupil slightly dilated
•No NCV this time : neurologist do other
test also

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Case 6
•Diagnosis ? Diabetic ophthalmoplegia
•MRI Brain : Normal
•Do we all agree

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Rethink Diagnosis
•Aneurysm
•Aneurysm
•Diabetic ophthalmoparesis : pupil spared
•Myasthenia
•Thyroid ophtalmoplegia

46. 46
Cardiac Autonomic Neuropathy
•Prevalance 2.5 – 50 %
•Diagnosis : HR/ BP response to breathing ,
valsalva posture . 2 tests must be positive
•Postural hypotension indicates severe
involvement. 24 Hr ambulatory BP useful
•Treatment/ prevention : Glycaemic control,
Hyperlipidemia control, Anti hypertensives.
Microalbuminuria

47. 47
Gastrointestinal Autonomic
Neuropathy
•Symptoms/Signs 40/50%
–Gastroparesis/ reflux
–Diabetic enteropathy resulting in diarrhea and constipation
–May cause postprandial hypotension and hypoglyaemia
–Diagnosis : Scintigraphy/ USG monitoring
•Treatment
–Other causes of gastroparesis or enteropathy should first
be ruled out
–Gastroparesis - Small, frequent meals, metoclopramide,
erythromycin, lesuride, itopride
–Enteropathy - loperamide, antibiotics, stool softeners or
dietary fiber

48. 48
Genitourinary Autonomic
Neuropathy
Sign/Symptom Treatment
Bladder dysfunction Voluntary urination;
catheterization
Retrograde ejaculationAntihistamine
Erectile dysfunction Sildenafil, tadalafil
Dyspareunia Lubricants; estrogen
creams

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Treatment
•Management of neuropathy
•Management of Pain

50. 50
Glycaemic control
•Good Glycaemic control reduces risk by
60% in IDDM
•NIIDM unclear

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Alphalipoic acid
•Intravenous alphalipoic acid : 3 trials
patients 25% vs 16% significant response
•Oral alphalipoic acid 600-1800mg
significant benefit (diabetes care 2006)

52. 52
Aldose reductase Inhibitors
•Metanalysis 13 studies 1800 patients
tolrestat , zenrestat : no benefit (cochrane
2008)

53. 53
Epalrestat
•Aldose reductase inhibitor
•6 clinical trials show benefit on MNCV , SNCV
and subjective symptoms .
• 3 year trial shows sustained efficacy over placebo
•Dose 50mg tds
•Side effects : nausea vomiting , raised liver
enzymes
•More Robust data required.

54. 54
Epalrestat
•Epalrestat : Best benefit early diabetes Mild
to moderate diabetes
•Fidarestat and Ranirestat are under trials

55. 55
Vitamin B 12
•One trial of 100 patients B 12 significantly
better than nortryptiline
•Metaanalysis ; 7 trials 2 good quality 5 poor
quality
• Subjective symptom improvement no
electrophysiological changes ( Acta Neurol
Tai 2005)

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Management of Pain
•Troubled patient
•Troubled doctor

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Therapies to reduce pain
•Analgesics
•Antidepressants – TCAs
•Duloxetine
•Anticonvulsants – Carbamazepine
•Gabapentin
•Pregabalin

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Neuropathic pain : Treatment
Anti depressants ; 4 Meta analysis (1996,1999,2000, 2005)
Imipramine ( 50-350mg /Day) , 5 Trials , 4 Trials
Amytriptiline (25-150mg), 1 trial, 2 Trials
Desipramine (12.5-150mg) 1Trial, 2 Trials
Fluoxetine (20-40Mg) 1Trial, 2 Trials
Citalopram ( 20-40mg) 1Trial, 2 Trials
Paroxetine (40mg) 1Trial, 2 Trials
Mianserine (60mg) 2 Trials
Nortryptyline (25-100mg) 1Trial, 2 Trials
Maprotiline 1Trial, 2 Trials
Clomipramine (150mg ) 1Trial, 2 Trials
Follow up 2-6 weeks ( Mc Quay Pain 1996 217-27, Collins J Pain Sym M
anage 2000 449-58)

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Neuropathic pain :Antidepressants
Trials No A %imp A %imp P OR NNT
A 12 491 66% 36% 1.7(1.4-1.9) 3.4(2.6-4.7)
TCA 8 283 1.9(1.5-2.3) 3.5(2.5-5.6)
SSRI 3 162 1.3( 1.0-1.8)
A 13 400/373 69.2% , 41% 3.0 (2.4-4)
TCA 8 3.2(2.3-3.8)
A 12 3.0(2.4-4.0)
TCA 2.4( 2.0-3.0)
TCA C 2.0( 1.7-2.5)
TCA Nor 3.4( 2.4-3.6)
SSRI 6.7( 3.4-435)
(Mc Quay Pain 1996 217-27, Collins J Pain Sym Manage 2000 449-58, Sindrup Pain
1999 389-400)

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Antidepressants : Adverse affects
Trials No A % harm A %harm P OR NNH
A 7 70% 33% 2.3(1.8-2.9) 2.7(2.1-3.9)
TCA 5 72% 40% 2.0(1.6-2.6) 3.2(2.3-5.2)
Major Harm
A 16 8% 1% 2.6(1.4-5) 17(10-43)
TCA 11 10% 3 % 2.8(1.4-5.9) 14(8.5-38)
SSRI 2 5% 0% 10(.1->1000)
A 71% 43% 12.6(5.6-30) 2.8(2-4.7)
Major Harm
A 8% 2.8% 3.3(1.4-7.8) 19.1(11-74.4)
(Mc Quay Pain 1996 217-27, Collins J Pain Sym Manage 2000 449-58)

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Antidepressants – TCAs
•Not approved DPN & PHN
•Small therapeutic-toxic
window
•4-6 weeks
•Sexual adverse effects
•QT prolongation
•Arrhythmias
•Anticholinergic side effects
•Postural Hypotension
•Caution for patients with cardiac
risk factors
MOA - Increase NE and 5-HT

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Duloxetine
•Efficacy : 2220 patients 3 trials RR 1.65
•NNT 6 ( Cochrane 2009)
•Duloxetine 1139 patients
• Inc B sugar modest, constipation , nausea ,
somnolence.

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Antidepressants – Duloxetine
•SNRIs
•US FDA – DPN only
•Hypertension
•Onset 1-2 weeks
•GI side effects
•Sexual adverse effects
MOA – Selective Serotonin Norepinephrine
Reuptake Inhibitor

64. 64
Neuropathic pain :Anticonvulsants
Trials No A %imp A %imp P OR NNT
A 3 321 62% 26% 2.4(1.8-3.2) 2.7(2.2-3.8)
CBZ 1 30 93% 63% 3.3 (2-9.4)
PHT 1 40 100% 25.7% 2.1 (1.5-3.6)
1 negative trial with phenytoin .
(Mc Quay BMJ 1995 1047-52, Collins J Pain Sym Manage 2000 449-58,
Mellegers et al Clin J Pain 2001)

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Anticonvulsants : adverse effects
Trials No A % harm A %harm P OR NNH
A 4/492 68% 24% 2.5(2-3.1) 2.7(2.2-3.4)

PH/CBZ 2 /98 40% 8% 4.2 (2-8.9) 3.2(2.1-6.3)
Major Harm
A 5/548 12% 7% 1.6(.97-2.7)
PH/CBZ 3 /98 5% 0% 13 (.3->500)
(Collins J Pain Sym Manage 2000 449-
58)

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Gabapentin
•7 trials 1468 patients NNT 2.9 NNH 3.7
•First-line drug for NeP
•No drug interaction
•Drawbacks
Bioavailability – 60%
Absorption – variable
Response – Variable (interindividual )
Dose - 1200 – 3600 mg/day (unpredictable)
Titration – 3-8 weeks

67. 67
Neuropathic pain :Anticonvulsants
Topiramate 4 RCTs
3 18-22 week trials with dose 100-400mg /day with 1269
patients showed better improvement in topiramate group but
none was significant.
24% patients in topiramate group withdrew due to side effects 1
12 week trial 214 patients with higher pain score showed
significant improvement ( p=.04) (Thienel Acta Neurol Scand
2003 :221-31)
Lamotrigine : Benefit seen in open studies but no controlled
trials . ( 1 RCT in HIV neuropathy showed benefit )
Oxcarbezepine has shown equivalent efficacy with CBZ in 3
RCTs with less side effects (45%vs 62.5 %)

68. 68
Anticonvulsants
Carbamazepine
1.FDA approved for Trigeminal Neuralgia
2.Side effects
Oxcarbazepine
1.One study for NeP
2.Hyponatremia – monitoring of serum
sodium required
3.Rash – 4 %
4.Few Drug-drug interaction
Levetiracetam
1.No controlled studies
Tiagabine
1.No controlled studies
Lamotrigine
1.Rash 10%
2.Insomnia
Topiramate
1.Nagative results (3 - / 1 +)
2.Weight loss (10-20%)
3.Cognitive impairment
4.Nephrolithiasis (1.5%)
Valproate
1.Nausea
2.Sedation
3.Fatal Hepatotoxicity –
4. Hair loss
5.Hematologic effect (Platelet)
6.Drug-drug interactions

69. 69
PREGABALIN
•Novel analgesic, anticonvulsant & anxiolytic properties works
on alpha 2 subunit of voltage gated calcium channels
•US FDA Approved (Dec 31, 2004) Rx for DPN / PHN and
adjunct in mgt of partial seizures (adults)

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Pregabalin
•Efficacy : 728 patients 3 trials RR 4.65
•( Cochrane 2009)
•Long term 3 year data available

71. 71
Favorable Safety and tolerability
•Pregabalin is well tolerated.
•Most adverse events are mild to moderate in intensity, occur during the
first week of treatment, and tend to resolve over time
•Discontinuation rates were low.
•No cardiovascular, ophthalmologic, renal, hepatic or neurological
concerns were noted in studies.
•Regarding diabetes control, pregabalin had no effect on glycosylated
hemoglobin A
1c.

 

72. 72
Neuropathic Pain :Opiates
. Tramadol : Metanalysis of 3 trials with 1 94 patients .
OR 4.9 (95% CI 2.5 to 9.8). , NNT 3.5 (95% CI 2.4 to 5.9).
2 poor quality trials with clomipramine and morphine
suggest equal efficacy (Dühmke RM, The Cochrane Database
of Systematic Reviews 2004, Issue 2. Art. No.: CD003726 )
Oxycodone : A trial of oxycodene with 330 patient showed
oxycodone plus gabapentin is better than gabapentin and
placebo

73. 73
Neuropathic Pain :Drugs
Capsaicin : Meta analysis of 3 RCT with total 377 patients
treated for 8 wks with capsiacin cream .075% .
Pooled OR 2.74 ( CI 1.73-4.32), NNT -5.9 (Zhang etal Eur J
Clin Pharm.1994517-22)
Levodopa ; Levodopa + benzeraside (100+25 ) TID for 28 days
significant at p=.004 . NNT 3.4 ( Ertas Pain 1998 257-59)
Transdermal clonidine; 12/41 responders (Michael Pain 1995 267-74)
Mexilitine ; 3 RCTs have shown significaant benefits with anti
arrythmic drug .
Fleicenide ; significant arrythmic effects

74. 74
Neuropathic pain : Treatment
Anti depressants ; Meta analysis (65 trials )
12 000 patients 27 drugs
Amytriptiline , SMD -0.72 (- 1.35 to – 0.08) 1 trial, 2 Trials
Duloxetine SMD -1.38 ( -1.82- -0.86)
Venlafaxine SMD – 1.53 ( -2.51 to -0.56 )
Carbamazepine SMD -1.57( -2.83 To -0.31)
SNRI better than anticonvulsants
Amytriptiline better than topical Capsicain
( Greibler Ann of Int med Nov 639-649 )

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TENS
•TENS Three trials 78 patients Subjective
improvement . Short term benefit .
•Conclusion : larger Trials Needed (Diab
Res Clin Pract 2010)

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Team of Three
•Pregabalin, methylcobalamin, (most useful form of
vitamin B12 for Neuropathy); and alpha-lipoic acid (a
potent antioxidant).
•
•Combined formulations are aimed at ensuring normal
neuronal function in patients with neuropathic pain

77. 77
Winning combination
• Pregabalin analgesia is unaffected by methylcobalamin and alpha-lipoic
acid, and repeated administration of Pregabalin does not lead to analgesic
tolerance.
•Most methylcobalamin-related adverse effects rarely occur with Pregabalin ,
suggesting that most adverse effects would not “overlap” if the drug were used
in combination with Pregabalin .
•Clinical and postmarketing surveillance studies have indicated that alpha-
lipoic acid has a favorable side effect profile. Adverse effects are mild.
•Pharmacokinetics of alpha-lipoic acid are not influenced by creatinine
clearance and are unaffected in subjects with severely reduced kidney function
or end-stage renal disease.
•Thus, a combination of alpha-lipoic acid, pregabalin and methylcobalamin
may provide more additive effect for analgesia.

78. 78
Power and promise of pregabalin
• Pregabalin modulates alpha
2delta calcium-channel subunits, a mechanism
thought to be important in neuropathic pain.
•Pregabalin is now widely used for neuropathic symptoms.
•Pregabalin ameliorates pain associated with neuropathy with few side
effects and sleep interference associated with diabetic peripheral neuropathy
and exhibits positive effects on mood and quality of life.
•When compared head-to-head with amitriptyline, pregabalin had better
efficacy with favorable safety profile.
•The side-effect profile of pregabalin is more favorable than those of many
other agents.
•That is why experts consider pregabalin to be a reasonable first choice on
the basis of clinical trials showing efficacy and its relatively favorable side
effect and pharmacokinetic profile.

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Rationale
•Methylcobalamin is the neurologically active form of
vitamin B12.
•The liver does not convert cyanocobalamin, the commonly
available form of vitamin B12, into adequate amounts of
methylcobalamin, which the body uses to treat or correct
neurological defects.
•Studies have shown that high doses of methylcobalalmin
are effective in neuron regeneration and that there is no
known toxicity at these doses.

80. 80
Methylcobalamin advantages
• Promotes myelination
•Improves axonal transport and regeneration
•Promotes nucleic acid & protein synthesis
•Restores delayed synaptic transmission

81. 81
MethylCobalamin
Vit B12 = Cyanocobalamin
Adenosylcobalamin Methylcobalamin
Folate
Metabolism Phospholipids
Myelin
= Conversion Impaired with Advancing Age

82. 82
Methylcobalamin: Role
Phosphatidylcholine
Homocysteine
Myelin Basic Protein (MBP)
S-Adenosylmethionine
Methionine
Methylcobalamine
Spingomyelin
Methionine
Synthase

83. 83
ALA: Broadspectrum
Antioxidant Actions
Unlike other antioxidants, which work only in
water or fatty tissues, lipoic acid is unusual in
that it functions in both water and fat.
By comparison, vitamin E works only in fat and
vitamin C works only in water.
This gives lipoic acid an unusually broad
spectrum of antioxidant action.

84. 84
ALA: Smart Antioxidant
Actions
Antioxidants are a bit like kamikaze pilots, sacrificing
themselves to knock out free radicals.
ALA & its reduced metabolite DHLA scavenge
various free radicals
α-lipoic acid increase intracellular glutathione and
coenzyme Q10 levels.
Provided additional antioxidant activity by recycling Vitamin-
C, ubiquinones & glutathione
In addition, lipoic acid may be able to do the work of
other antioxidants when the body is deficient in them.

85. 85
Pregabalin + Mecobalamin + ALA

Containdication
Hypersensitivity to any of the ingredients of
Formulation
Pregnancy & Lactation
Use in Pregnancy … Not established
Lactation … Only if benefit outweighs risk

86. 86

Side Effects
Pregabalin: Somnolence & Dizziness
MetCob: Anorexia, nausea/vomiting
Dosage & Admin.
One tab. BID
Dose should be individualized
Pregabalin + Mecobalamin + ALA

87. 87
Benefits Neuropathy ...
PregabalinMeCob ALA
Pain Relief
Repairing Effects
Protection from
Oxidation Stress

88. 88
Clinical scenario 1
•So a patient comes with diabetic neuropathy with severe
pain in the leg on pregabalin 225 mg/ day without relief
what would you add / do
•Add gabapentin/ change
•Increase dose
•Add oxcarbazepine
•Add tryptomer  

89. 89
Case 1
•MR RG 65 year male diabetic for 20 years
presented with progressive difficulty in
climbing stairs , pain legs burning since
last many months
•Examination ; Proximal weakness > Distal ,
decreased ankle jerks rest normal mild
sensory loss

90. 90
Case 1
•NCV mild decrease in conduction velocity
in all sensory nerves report compatible with
diabetic neuropathy
•Diagnosis

91. 91
Case 1
•Management
•Epalrestat
•Alphalipoic acid/ B12
•TCA
•Anticonvulsant

92. 92
Case 1
•No improvement
•Now what

93. 93
Rethink Diagnosis
•Motor weakness Still Motor NCV normal ?
•Do EMG : Myopathic
•CPK raised
•Muscle biopsy : polymyositis
•Treated with IVIG better

94. 94
Take Home Message
•All weaknesses in lower limbs in Diabetic is
not neuropathy .
•Even IN MND in diabetics NCV may show
sensory abnormalities
•Evaluate clinically and with EMG if motor
weakness occurs.

95. 95
Take Home Summary
•Tricyclic antidepressants, Duloxetine, Carbamazepine,
Gabapentin ,pregabalin and Topical capsiacin are
effective therapies for pain management in
neuropathies.
•However with each of them there are limitations
•The efficacy of all the drugs is largely similar
•Epalrestat, alphalipoic acid , vitamin B12 may help
reducing neuropathy

96. 96
Summary
•Add drugs which combine different targets for better
action .
•Therefore combination of pregabalin methylcobalamine
and alphalipoic acid gives twin benefits
•Do not discard drugs at lo w doses , titrate to higher
doses for optimal benefit
•The drug s can cause short inconvenience and side effects

97. 97
Summary
•Educate the patient about them
• Indian patients may require lower doses as compared to
studies in western populations .
•Treat the patient as a whole addressing all the important
cofactors like stress, psychosocial considerations and
counsel adequately

98. 98