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Diabeticneuropathy
1.
2. An internationally agreed simple definition of Diabetic neuropathy for
clinical practice is
โthe presence of symptoms and/or signs of peripheral
nerve dysfunction in people with diabetes after the
exclusion of other causesโ
BoultonAJ et al. Diabetic neuropathies: a statement by
theAmerican DiabetesAssociation. Diabetes Care. 2005Apr;28(4):956-62.
3. โdiabetic neuropathy is a descriptive term meaning a
demonstrable disorder, either clinically evident or subclinical,
that occurs in the setting of diabetes mellitus without other
causes for peripheral neuropathy. The neuropathic disorder
includes manifestations in the somatic and/or autonomic parts of
the peripheral nervous systemโ
American Diabetes Association, American Academy of Neurology: Report and recommendations of the San
Antonio Conference on Diabetic Neuropathy (Consensus Statement). Diabetes Care 11:592โ597, 1988
5. ๐ DM risen over past two decades, 30 million in 1985 to 285 million in
2010.
๐ IDF projects 438 million in 2030.
๐ All forms of diabetes of sufficient duration are vulnerable
๐May coincide with CIDP, v B12 deficiency, alcoholic neuropathy, endocrine
neuropathies.
๐ Additional causes in 10% to 55% of patients with DM.
6. Pirartโs cohort of 4400 diabetics - prevalence 45% after 25 years.
๐ Can occur with IGT and metabolic syndrome without hyperglycemia.
๐ Most common form of neuropathy in the developed countries.
๐ More hospitalizations than alldiabetic complications
๐
50% to 75% of nontrauma amputations.
๐ Weakness and ataxia, likelihood of falling 15 times unaffected.
7. ๐
๐90% positive on sophisticated tests of autonomic function or
peripheral sensation.
๐ Major morbidity is foot ulceration, gangrene ,limb loss.
๐ Amputation risk 1.7-fold , 12-fold if deformity (consequence of
neuropathy), 36-fold if h/ o ulceration.
8. Modifiable Risk Factors Non-modifiable Risk Factors
๐ Poor glycemic control
(Elevated HbA1c)
Alcohol
Hypertension
Cigarette Smoking
Hypertriglyceridemia
๐
๐
๐
๐
๐
๐
๐
๐
๐
Obesity
Older age
Male sex
Height
Family h/o neuropathic
disease
Longer duration of diabetes
APOE genotype
Aldose reductase gene
hyperactivity
Angiotensin-converting
enzyme genotype
๐
๐
๐
๐
1.Harati Y. Diabetic Neuropathies: Unanswered Questions. Neurol Clin 25 (2007) 303โ317
2.Tesfaye S, Chaturvedi N, Eaton SE, et al. Vascular risk factors and diabetic
neuropathy. N Engl J Med 2005;352(4):341.
9. Hyperglycemia
๐ Rheological changes - increase endoneurial vascular resistance and reduce
nerve blood flow.
๐ Depletion of nerve myoinositol by competitive uptake & activates protein
kinase C
๐ Activates polyol pathway in nerve tissue through aldose reductase
๐ Accumulation of sorbitol and fructose in nerve
๐ Nonenzymatic glycosylation of structural nerve proteins
.
๐ Glucose auto-oxidation- toxic reactive oxygen intermediates .
10.
11.
12.
13. Abnormal sural nerve recording from a patient with diabetic neuropathy showing a decreased sural sensory
nerve action potential amplitude (normal >6 ยตV) and slow sural sensory nerve conduction velocity (normal
>39 m sโ1; panel a). Intraepidermal nerve fibres (arrows) and branched fibres (arrowhead) in a skin biopsy sample
from a healthy individual (panel b) and from a patient with small-fibre neuropathy (panel c). A sural nerve
biopsy sample exhibiting evidence of axonal loss of small-diameter and large-diameter nerves in diabetic
neuropathy (panel d). Image (ร20 magnification) of an Epon-embedded, 0.5 ยตm thick section stained with
toluidine blue (panel d). AMP, amplitude; CV, conduction velocity; Dist, distance; Lat, latency; NCS, nerve
conduction studies; Rec, recording; Stim, stimulating. Parts b and c adapted from ref.232, Springer Nature Limited.
16. S U R A L N E RV E B I O P S Y F R O M PAT I E NT WITH D I A B E T I C LU M B A R
R A D I C U LO P L E XO PAT H Y.
Perivascular lymphocytic inflammation involves two epineurial arterioles.
(Hematoxylin and eosin, ร25.) B, In the same patient, semi- thin transverse section
illustrates selective involvement of one fascicle, with marked loss of myelinated
fibers, a pattern highly suggestive of nerve ischemia.
17. ๐Generalized Symmetrical Polyneuropathies Distal
sensory or sensorimotor polyneuropathy Small-fiber
neuropathy
Autonomic neuropathy
Large-fiber sensory neuropathy
๐Focal and Asymmetrical Neuropathies Cranial
neuropathy (single or multiple) Truncal neuropathy
(thoracic radiculopathy) Limb mononeuropathy (single
or multiple)
Proximal motor neuropathy (lumbosacral radiculoplexopathy, amyotrophy)
๐Combinations
Polyradiculoneuropathy Diabetic
neuropathic cachexia
18.
19. DISTAL SYMMETRICAL POLYNEUROPATHY
A. Acute sensory neuropathy
๐ Burning discomfort in feet, hyperesthesiae, deep aching pain
๐ Sharp, stabbing or โelectric shockโ like sensations in lower limbs.
๐ Weight loss, depression, erectile dysfunction
๐ Nocturnal exacerbation,Clothes irritating hyperesthetic skin.
๐ Allodynia on sensory testing, a normal motor exam,reduced ankle reflexes.
๐ Poor glycemic control , may follow an episode of ketoacidosis
๐ Associated with weight losss & eating disorders .
20. ๐ Blood glucose flux in genesis of neuropathic pain .
๐ Degeneration of myelinated & unmyelinated fibers
๐ More common in DM with mitochondrial tRNA mutation at 3243
(Suzuki , 1997)
๐Neural ischemia by sudden improvement of glycemic control, โstealโ
effect with arteriovenous shunting
๐ In management, stable blood glucose control is most important.
๐ Onset acute or subacute, severe symptoms resolve in less than a year
21. ๐ Most common DN,3/4TH of all DN.
๐ Sensory predominant, autonomic correlate with severity
๐ Minor involvement of distal muscles of lower extremities.
๐ Sensory stocking-glove distribution
๐ Length-dependent pattern.
๐ Advanced- sensation impaired
over area.
chest & abdomen - wedge-shaped
22. ๐ Painless paresthesias beginning at the toes and feet,
๐ Impaired vibration & JPS
๐ Diminished reflexes.
๐ Ataxia secondary to sensory deafferentation.
๐ Often asymptomatic, sensory deficit on examination.
Small-fiber neuropathy
๐ Deep, burning, stinging, aching pain ;allodynia to light touch.
๐ Pain & temp impaired, relative preservation of vibration & JPS & DTR
๐ Often accompanied by autonomic neuropathy
๐ May develop soon after onset of IDDM.
23. ๐ Distal joint destruction (acrodystrophic neuropathy).
๐Chronic foot ulceration (4% to 10%) due to unnoticed tissue damage, vascular
insufficiency, secondary infection
๐ Neuropathic arthropathy(Charcot joint ) in patients with foot ulcers &
autonomic impairment,
๐ Small joints of feet.
๐Diabetic pseudotabes - lancinating pains, loss of JPS , diabetic pupillary
abnormalities (pseudo-Argyll Robertson pupils).
24. ๐ Absent or decreased amplitudes of sural SNAPs
๐ Low amplitude or absent tibial H-reflexes .
๐Active denervation in intrinsic foot muscles or decreased amplitudes of
CMAPs
๐ Slowing of motor conduction velocities, in 2/3 rd patients.
25. ๐CIDP, MGUS, circulating GM1 antibodies and antibodies to
neuronal cells, and inflammatory vasculitis .
๐ Vinik et al - half of patients with proximal neuropathies have a
vasculitis,
๐ 9% have CIDP, MGUS, ganglioside antibody syndrome
Sharma et al- CIDP 11 times more frequent among diabetics
๐
๐ If demyelinating, CIDP should be considered.
๐ CIDP responds to intervention
Sharma K, Cross J, Farronay O, et al. Demyelinating neuropathy in diabetes mellitus. Arch
Neurol 2002;59:758โ65
26.
27. ๐
๐Difficulties in distinguishing between diabetic
polyneuropathy and CIDP
1) Overlap of the clinical features
2)CSF protein often elevated in DM
3)EDX may show demyelination in DM
4)Nerve biopsies show varying axonal and demyelinating changes in
both conditions.
28. ๐ Correlates with severity of somatic neuropathy.
๐ Subclinical impairment CVS , GI , GU dysfunction
๐Orthostatic hypotension, resting tachycardia, diminished heart-rate response
to respiration
๐ Vagal denervation of heart- high resting pulse & loss of sinus arrhythmia.
๐ Painless or silent myocardial
infarction.
29. ๐ Delayed gastric emptying - nausea, early satiety, postprandial
bloating.
๐Diabetic diarrhea due to small-intestinal involvement , at night,
paroxysmal.
๐ Constipation due to colonic hypomotility is more common than diarrhea.
๐ Bacterial overgrowth may occur.
30. ๐ Impaired bladder sensation - first symptom of GU dysfunction.
๐ Bladder atony - prolonged intervals between voiding, urinary retention,
overflow incontinence.
๐ Void every few hours to prevent urinary retention.
๐ Impotence is often first manifestation in men , occurring in more than 60%.
๐ Both erectile failure and retrograde ejaculation.
๐ Impotence usually associated with distal symmetrical polyneuropathy.
31. ๐ Sudomotor abnormalities - distal anhidrosis, facial and truncal sweating,
heat intolerance.
๐ Gustatory sweating - profuse sweating in face following food .
๐ Pupillary abnormalities - constricted pupils with sluggish light reaction, in
20% .
๐Blunted response to hypoglycemia - inadequate sympathetic & adrenal
response - unawareness of hypoglycemia โcomplicates intensive insulin
treatment
32. ๐ Diabetic proximal neuropathy,. Diabetic amyotrophy, thoracic radiculopathy,
and proximal or diffuse lower extremity weakness -different presentations of
involvement of roots or proximal nerve segments.
๐Asymmetrical weakness and wasting of pelvifemoral muscles may occur
abruptly or stepwise in individuals with diabetes older than 50 .
๐ May develop with long-standing NIDDM during poor metabolic control
and weight loss, but can occur in mild and well-
controlled diabetics or be presenting feature.
33. ๐ Unilateral severe pain in the lower back, hip, and anterior thigh heralds onset
๐ Within days to weeks, weakness of proximal and, to a lesser extent, distal
lower-extremity muscles (iliopsoas, gluteus, thigh adductor, quadriceps,
hamstring, and anterior tibialis).
๐ Opposite leg affected after days to months.
๐ Reduced or absent knee and ankle jerks.
๐ Weight loss in more than half & more than nondiabetic
lumbosacral radiculoplexopathy
34. ๐
๐ Recovery takes up to 24 months due to slow axonal regeneration, mild to moderate
weakness may persist.
๐EMG - low-amplitude femoral nerve motor responses, fibrillation potentials in
thoracic and lumbar paraspinal muscles, active denervation in affected
muscles.
๐Neuroimaging should be considered when lumbar root, cauda lesions, or
structural lumbosacral plexopathy suspected .
๐ No effect of corticosteroids in recovery of motor deficit.
35. ๐ T4 -T12 radiculopathy - pain or dysesthesias in distribution.
๐ Bulging of abdominal wall due to weakness of abdominal muscles
๐ In isolation or with lumbosacral radiculoplexopathy.
๐ Can mimic intraabdominal, intrathoracic, or intraspinal disease, zoster .
๐ May persist for several months before resolution within 4 to 6 months.
๐ EDX - active denervation in paraspinal and abdominal muscles,
๐ Focal anhidrosis in area of pain with thermoregulatory sweat test.
36. ๐ Nerve infarction or entrapment.
๐Infarction- abrupt onset of pain , variable weakness and atrophy. Median, ulnar,
fibular n. commonly affected.
๐ Entrapment more common than infarction.
๐EDX - axonal loss in nerve infarction ; conduction block or slowing in
entrapment.
๐ DM in 8% to 12% of patients with CTS.
๐ Aggravation of ischemia in nerves with chronic endoneurial hypoxia.
37. ๐ Mononeuritis multiplex- replaced as rarely due to inflammation
๐ Involvement of two or more nerves
๐ Onset abrupt in one nerve, other nerves are involved sequentially
๐Multiple mononeuropathies involving proximal nerves considered cause of
amyotrophy.
๐ Infarction results occlusion of vasa nervorum.
๐ Systemic vasculitis be considered in D/D
38. ๐ 3 rd nerve palsy is most common
๐Pupillary sparing, from ischemic infarction of the centrifascicular
oculomotor axons
๐ Peripheral pupillary motor fibers spared due to collateral circulation
๐ 4th , 6th, 7th nerves also affected.
๐ Bell palsy- higher frequency of diabetes.
๐ Rhinocerebral mucormycosis and โmalignantโ external otitis
39. Vinik et al , Diabetic Neuropathy in Older Adults. Clin Geriatr Med 24 (2008) 407โ 435
40. Think if-
๐ Rapidly progressive
๐ Prominent motor abnormality or cranial nerve involvement
๐ Disproportionate large fiber
abnormalities.
๐ Involvement of the entire lower limbs without neuropathy of the
distal upper limb.
๐ More often sensory symptoms and findings in the hands
41. ๐ Scores to assess clinical signs pioneered by Dyck , who first described the
NDS and later the Neuropathy Impairment Score (NIS).
๐ Amodified NDS used in several studies , can be used in community
๐ Shown to be best predictor of foot ulceration and best neuropathic end point in a
large prospective community study
๐ The maximum NDS is 10, with a score of 6 or more being predictive of
foot ulcer risk.
42.
43. Semmes-Weinstein monofilament
๐Assesses pressure perception when gentle pressure is applied to the handle
sufficient to buckle the nylon filament.
๐ One that exerts 10 g pressure, is most commonly used
๐ Also referred as 5.07 monofilament .
Graduated Rydel-Seiffer tuning fork
๐ Visual optical illusion to determine intensity of residual vibration on a 0โ8
scale at the point of threshold (disappearance of sensation).
Tactile circumferential discriminator
๐ Assesses perception of calibrated change in the circumference of a probe
(a variation of two-point discrimination).
๐ Also demonstrated good agreement with other measures of QST.
44. Neuropen
๐Assesses pain using both a Neurotip at one end of the โpenโ and a 10-g
monofilament at other end.
๐ Was shown to be sensitive device for assessing nerve function when
compared with the simplified NDS
45. ๐NCV is only gradually diminished by DPN, with estimates of a loss of
0.5m/ s/ year.
๐ Sensitive but nonspecific index on onset
๐ Detecting subclinical deficits.
๐ Trace the progression.
๐ Changes related to glycemic control.
๐Can reflect pathology in large axons (Atrophy, demyelination,loss of
density)
๐ Can improve with effective therapy
46. Amplitudes, area, and duration. Peak
๐ Strong correlation (r 0.74; P 0.001) between myelinated fiber density
and whole-nerve sural amplitude in DPN
๐Loss of SNAP amplitude at a rate of 5% per year in DPN over 10-year
period
๐ Total area of the SNAP and CMAP suggested as means of assessing contribution of
slower conducting fibers,
๐ Area alone, or with peak amplitude, can be used to estimate temporal
dispersion and conduction block.
47. ๐ Resting heart rate
>100 bpm is abnormal.
๐ Beat-to-beat HRV
At rest and supine heart rate by ECG while patient breathes at 6/m
Difference of >15 bpm - normal, <10 bpm - abnormal.
Lowest normal value for the expiration-to-inspiration ratio of the R-R
interval is 1.17 in 20โ24 years of age.
Heart rate response to standing
R-R interval measured at beats 15 and 30 after standing.
Normally, tachy F.B. reflex brady. The 30:15 ratio is 1.03.
โ
โ
โ
๐
โ
โ
48. ๐ Heart rate response to the Valsalva maneuver
โ Exhales into manometer to 40 mmHg for 15 s
โ Healthy subjects develop tachy & peripheral vasoconstriction during strain &
overshoot brady, rise in BP with release.
โ The ratio of longest R-R to shortest R-R should be 1.2.
๐ Systolic blood pressure response to standing
โ Sys BP measured supine. Patient stands, BP aft 2 m.
โ Normal response- fall of <10 mmHg,
โ Borderline - fall of 10โ29 mmHg
โ Abnormal - fall of >30 mmHg with symptoms
49. ๐ Diastolic blood pressure response to isometric exercise
โ Squeeze handgrip dynamometer to a max . Then squeezed at 30% max for 5
min.
โ N response for diastolic BP is a rise of >16 mmHg in the other arm.
๐ ECG QT/QTc intervals
The QTc should be 440 ms.
๐ Neurovascular flow
โ Using noninvasive laser Doppler measures of peripheral sympathetic responses to
nociception.
๐ Radionuclide Cardiac Imaging
โ 123-I-metaiodobenzylguanidine (MIBG)
โ 11-C-hydroxyephedrine
50. Symptomatic management
1) Exclude nondiabetic causes
โ Malignant disease (e.g., bronchogenic carcinoma)
โ Metabolic
โ Toxic (e.g., alcohol)
โ Infective (e.g., HIV infection)
โ Iatrogenic (e.g., isoniazid, vinca alkaloids)
โ Medication related (chemotherapy, HIV treatment)
2) Explanation, support, and practical measures (e.g., bed cradle to lift bed, clothes
off hyperesthetic skin)
3) Assess level of blood glucose control profiles
4) Aim for optimal stable control
5) Consider pharmacological therapy
51. ๐ Open-label uncontrolled studies suggested near normoglycmia
helpful in painful neuropathic symptoms.
๐Stability of glycemic control equally important to level of achieved control.
๐ Lack of appropriately designed controlled studies
๐ Generally accepted that intensive diabetes therapy aimed at near
normoglycemia should be first step in the treatment of any form of DN.
52. ๐Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial-
(10,000 patients)-new cases of neuropathy significantly reduced intensive group
A DVA N C E trial โ( 11,000 patients)- (5y) not significantly affected by
intensive control
๐ Diabetes Control and Complication Trial (DCCT; 1995) โ
(5y) intensive management reduces neuropathy by 64%
๐ Benefit persisted for 8 years after DCCT
53. Several different patterns of neuropathy can present in individuals with diabetes. Of these, the most common is
distal symmetric polyneuropathy (DSP). Examples of patterns of neuropathy are DSP, small-fibre-predominant
neuropathy or treatment-induced neuropathy (part a); radiculoplexopathy or radiculopathy (part b);
mononeuropathy (part c); and autonomic neuropathy or treatment-induced neuropathy (part d). Small-fibre-
predominant neuropathy has the same distribution as DSP, although the neurological examination and results
from nerve conduction velocity studies are different. Diabetic radiculoplexopathy or radiculopathy can respond
to immunotherapy and usually improves with time, unlike other types of nerve injury in individuals with
diabetes. Treatment-induced neuropathy is under-recognized, is caused by overaggressive glycaemic control and
can present in multiple forms (parts a and d). Adapted by permission from BMJ Publishing Group Limited. BMJ
Peltier, A., Goutman, S. A. & Callaghan, B. C. 348, (2014)230
54. First-line and second-line treatments for painful diabetic neuropathy include several
drug classes, such as anticonvulsants (gabapentin or pregabalin), serotonin and
noradrenaline reuptake inhibitors (SNRIs; duloxetine or venlafaxine) and tricyclic
antidepressants (amitriptyline, nortriptyline, desipramine or imipramine). Opioids
should be avoided owing to their serious adverse effects and association with addiction.
55. ๐ No evidence to support NSAIDs.
Tricyclic drugs
๐ Several RCTs supported these agents in neuropathic pains.
Mechanisms
โข Inhibition of NE &/or 5-HT reuptake at synapses of central descending pain
control systems
โข Antagonism of NMDA rec mediating hyperalgesia & allodynia .
โข Rapid onset, suggests a mode of action not primarily relief of depression.
๐ use is restricted because of the frequency and severity of side effects.
56. ๐ Most experience with amitriptyline and imipramine.
๐ Can be taken once a day in the evening.
๐ Desipramine also useful drug ,better tolerated than amitriptyline
๐ Side effects
โข Drowsiness and lethargy
โข Anticholinergic side effects, particularly dry mouth
๐In cases of painful neuropathy resistant to tricyclic drugs, combination with
major tranquilizers
๐Amitriptyline and transcutaneous electrotherapy described in failed
monotherapy.
๐ Superior to that of tricyclic monotherapy plus sham electrotherapy
57. ๐ inhibit presynaptic reuptake of 5HT, not NE.
๐ Paroxetine but not fluoxetine associated with significant pain relief.
๐ Citalopram 40 mg/day was confirmed to be efficacious in relieving
neuropathic pain, but less effective than imipramine
๐ Side effects are less common with SSRIs.
58. ๐ Used for many years
๐ Limited evidence for phenytoin and carbamazepine in DN
๐ Gabapentin now widely used
๐In a large controlled trial, significant pain relief with reduced sleep
disturbance was reported using dosages of 900โ3,600 mg daily.
๐In a recent review of all the trials of gabapentin for neuropathic pain, it was
concluded that dosages of 1,800โ3,600 mg per day of this agent were
effective
๐ Lamotrigine - antiepileptic agent with at least two antinociceptive properties.
๐ In a randomized placebo controlled study, Eisenberg et al confirmed
the efficacy of this agent in patients with neuropathic pain.
59. ๐Mexilitine is a class 1B antiarrhythmic , structural analog of
lignocaine.
๐ Efficacy in neuropathic pain confirmed in controlled trials and
reviewed by Dejgard et al. and Jarvis and Coukell.
๐The dosage used in trials (up to 450 mg daily) is lower than that
used for arrhythmias;
๐ Regular ECG monitoring necessary
๐ Long-term use of mexilitine cannot be recommended.
60. ๐ Tramadol - opioidlike, centrally acting, nonnarcotic analgesic.
๐ Although first trial was 6 weeksโduration, subsequent follow-up study
suggested symptomatic relief could be maintained for at least 6 months
๐ Side effects common , similar to other opioid-like drugs.
๐Similarly, two randomized trials have confirmed the efficacy of controlled-
release oxycodone for neuropathic pain in diabetes
๐ Opioids such as oxycodone may be considered as add-on therapies for patients
failing to respond to nonopioid medications.
61. Topical nitrate
๐ A recent study suggested local application feet of isosorbide
dinitrate spray was effective in relieving overall pain & burning
discomfort
Capsaicin
๐ Alkaloid, in red pepper, depletes substance P and
reduces chemically induced pain.
๐Several controlled studies combined in meta-analyses seem to
provide some evidence of efficacy in diabetic neuropathic pain
๐
Only recommended for up to 8 weeks of treatment
๐ Useful in localized discomfort.
62. Acupuncture.
๐ Unmasked studies support its use .
๐ In recent report, benefits lasted 6 months, reduced use of other analgesics
๐Conduct of potential blinded studies of acupuncture is problematic; although a
placebo response is possible with acupuncture
Other physical therapies.
๐ Percutaneous nerve stimulation
๐ Static magnetic field therapy .
๐ Electrical spinal cord stimulation.
โ A case series of patients with severe painful neuropathy unresponsive to
conventional therapy suggested efficacy of using an implanted spinal cord
stimulator.
63. Anticonvulsants
๐ If clinically appropriate, pregabalin should be offered for the treatment of PDN
(Level A).
๐ Gabapentin and sodium valproate should be considered for the treatment of PDN
(Level B).
๐There is insufficient evidence to support or refute the use of topiramate for the
treatment of PDN (Level U).
๐Oxcarbazepine, lamotrigine, and lacosamide should probably not be considered
for the treatment of PDN (Level B).
Valproate may is potentially teratogenic, be avoided in women of childbearing age. Due to weight gain and
potential worsening of glycemic control, this drug is unlikely to be the first treatment choice for PDN.
64. ๐ Amitriptyline, venlafaxine, and duloxetine should be considered for the
treatment of PDN (Level B). Data are insufficient to recommend one of
these agents over the others.
๐ Venlafaxine may be added to gabapentin for a better response (Level C).
๐There is insufficient evidence to support or refute the use of desipramine,
imipramine, fluoxetine, or the combination of nortriptyline and
fluphenazine in the treatment of PDN (Level U).
65. ๐Dextromethorphan, morphine sulfate, tramadol, an
oxycodone should be considered for the treatment of PDN
(Level B). Data are insufficient to recommend one agent
over the other
โข The use of opioids for chronic nonmalignant pain has gained
credence over the last. Both tramadol and dextromethorphan
were associated with substantial adverse events (e.g., sedation,
nausea, and constipation).
The use of opioids can be associated with the development of
novel pain syndromes such as rebound headache.
Chronic use of opioids leads to tolerance and frequent escalation
of dose.
โข
โข
66. ๐Capsaicin and isosorbide dinitrate spray should be considered for the
treatment of PDN (Level B).
๐Clonidine, pentoxifylline, and mexiletine should probably not be considered
for the treatment of PDN (Level B).
๐ The Lidoderm patch may be considered for the treatment of PDN (Level C).
๐There is insufficient evidence to support or refute the usefulness of vitamins
and -lipoic acid in the treatment of PDN (Level U).
Although capsaicin has been effective in reducing pain in PDN clinical trials, many
patients are intolerant of the side effects, mainly burning pain on contact with
warm/hot water or in hot weather.
67. ๐ Percutaneous electrical nerve stimulation should be considered for
the treatment of PDN (Level B).
๐ Electromagnetic field treatment, low-intensity laser treatment, and
Reiki therapy should probably not be considered for the treatment of
PDN (Level B).
๐ Evidence is insufficient to support or refute the use of amitriptyline
plus electrotherapy for treatment of PDN (Level U).
68. V. Bril, J. England, G.M. Franklin, et al. Evidence-based guideline: Treatment of painful diabeticneuropathy : Report of
the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine,
and the American Academy of Physical Medicine and Rehabilitation .Neurology 76 May 17, 2011
69. ๐ Head of bed elevated 6 to 10 inches.
๐ Prevents salt & water losses during night and combat supine hypertension.
๐ Two cups of strong coffee or tea with meals
๐ Frequent small meals
๐ Daily fluid intake (>20 oz/day) and salt ingestion (10-20 g/day).
๐Elastic body stockings may be beneficial by reducing the venous capacitance in
bed but poorly tolerated.
๐ Plasma volume expansion can by fludrocortisone (0.1-0.6 mg/day).
70. ๐ Phenylpropanolamine (25-50 mg TDS), once used to manage OH
๐ Midodrine, an ฮฑ1-adrenergic agonist,causes vasoconstriction, also effective.
๐Subcutaneous recombinant human erythropoietin effective in some patients
with OH & anemia.
๐ Octreotide may improve OH by splanchnic vasoconstriction.
๐ Delayed gastric emptying relieved with metoclopramide
๐ Diabetic diarrhea treated with short courses of tetracycline or erythromycin
๐ Clonidine reported to reduce troublesome diarrhea.
71. Aldose Reductase Inhibitors.
๐The first clinical trials of ARIs in DN took place 25 years ago, and
currently only one agent is available in one country (Epalrestat in
Japan) .
๐ Most of the early trials can be summarized as:
โ Too small. โ Too few โ Too short. โ Too late.
72.
73. FROM BOULTON A, VINIK, A, AREZZO J , ET AL. AMERICAN DIABETES
ASSOCIATION: POSITION STATEMENT: DIABETIC NEUROPATHIES. 2005.
74. ๐ ฮฑ -LA- potential efficacy for both symptoms & modifying
natura
l history . (ALADIN II, ALADIN III, SYDNEY)
๐ Two large North American/European clinical trials of of ฮฑ -LA are
in progress
๐ ฮณ-LA(GLA) , component of evening primrose oil, can prevent
abnormalities in diabetes and in essential fatty acid and
prostanoid metabolism
๐
GLA treatment for 1 year in a randomized trial resulted in
improvement in electrophysiology and deficits
75. ๏จ Studies of aminoguanidine, which inhibits the formation of AGEs,
mainly focused on nephropathy
๏จ ๐Few data are available on aminoguanidine or other inhibitors of AGE formation
in clinical neuropathy
๐
๐
Intracellular hyperglycemia increases DAG levels, which activates
PKC formation
๐Preliminary data suggest that treatment with a PKC- inhibitor might
ameliorate measures of nerve function in DPN . Multicenter trials
are currently in progress
76. Vasodilators.
๐Treatment with ACE inhibitors has been shown to improve
electophysiological measures of nerve function in mild neuropathy .
๐The short-acting vasodilator isosorbide dinitrate has been shown to
improve painful symptoms, but its effect on deficits and
electrophysiology are unknown
77. ๐Diabetic neuropathy occurs in about 45% patients with Diabetes
Mellitus
๐ Metabolic and Vascular factors are implicated in pathogenesis.
๐Most common type is distal symmetrical sensorimotor
polyneuropathy
๐ Exclude nondiabetic etiologies
๐ Stabilize glycemic control
๐ Tricyclic drugs (eg, amitriptyline 25 to 150 mg before bed)
๐ Anticonvulsants (eg, gabapentin, typical dose 1.8 g/day)
๐ Opioid or opioid-like drugs (eg, tramadol or controlled
release oxycodone)
๐Drugs targeting pathogenic process are in development and may be
available in near future.
78. ๐ Katirji B, Koontz D. Disorders of Peripheral Nerves. In:
Bradleyโs Neurology in Clinical Practice. 5thEdition.
๐ Harrisonโs Principles of Internal Medicine. 18th Edition.
๐ Harati Y. Diabetic Neuropathies: Unanswered Questions.
Neurol Clin 25 (2007) 303โ317.
๐ Vinik A I et al. Diabetic Autonomic Neuropathy. Diabetes Care,
Volume 26, Number 5, May 2003
Boulton AJM. Diabetic Neuropathies:A statement by the American
Diabetes Association. Diabetes Care, Volume 28, Number 4,
April 2005.
Vinik AI et al. Diabetic Neuropathy in Older Adults. Clin
Geriatr Med 24 (2008) 407โ435.
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