Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Three pronged approach to migraine epilepsy and neuropathic pain–role of oxcarbamazepine
1. Prof. A.V. SRINIVASAN
INSTITUTE OF NEUROLOGY
MADRAS MEDICAL COLLEGE
CHENNAI.3
Three Pronged Approach to
Migraine, Epilepsy and
Neuropathic Pain –
Role of Oxcarbamazepine
19-09-2004, Thrissur, Kerala
3. Prevalence
•Increases in both males and females from age 12
until approximately age 40.
Age •Peaks between ages 35 to 40 years.
•Continues to be higher in women (>2:1 ratio) after
the age of menopause.
•25% experience 4 or more severe attacks/month.
Frequency
•35% experience 1-3 severe attacks/month.
•40% experience 1 or < 1 severe attack/month.
•occurs about 3 times more often in women than men
Gender •Women between the ages of 30 and 49 years from
lower income households are at higher risk
Headache. 1994;319-328., JAMA. 1992;267:64-69.
4. Classification
International Headache Society
Migraine Migraine with aura Ophthalmoplegic Retinal
without aura migraine migraine
(Classical migraine)
(Common
migraine)
•Migraine with typical aura
•Migraine with prolonged aura
•Familial hemiplegic migraine
•Basilar migraine
•Migraine aura without headache
•Migraine with acute onset aura
Neurology. 1994; 44(suppl 4):S6-S10.
5. Migraine
attack Trigger
Increased serotonergic and noradrenergic
stimulation in the brain stem
Dilation or constriction of cerebral and
scalp blood vessels
Stimulation of branches of 5th cranial
nerve (Trigeminal)
Thalamus Chemoreceptor Nausea
Cortex Vomiting
Pain Hypothalamus - Photophobia
J of Pharmacy Practice, Dec 1993; 253-270
6. Co-morbidities
Comorbidity - presence of two or more disorders
whose association is more likely than chance.
Mood Neurologic Others
disorders disorders
Allergy/Asthma
Depression Epilepsy
GI disorders
Mania Essential tremor (ulcer, IBD)
Anxiety Stroke
Panic
Discipline Weighs ounces
Regret weighs Tons
7. Migralepsy
Migraine aura Seizures
(headache) Migralepsy
Both chronic neurologic
disorders with episodic
attacks
Migraine and epilepsy
Common symptoms
Some people feel the rain;
Others just get wet
8. Migralepsy
The Migraine – Epilepsy prevalence
Risk higher in patients who get migraines with aura,
compared with patients who get migraine without aura.
Median prevalence of epilepsy in migraineurs - 6%
Median prevalence of epilepsy in general population – 0.5%
Patients with partial and generalized forms of epilepsy are
more likely to have migraines, with the biggest increase--
fourfold--in those with posttraumatic epilepsy.
Family Pratice News, March 15, 2001
Opinion is ultimately determined by the feelings
and not by the intellect
9. Migralepsy
Migraine and epilepsy
a bi-directional relationship
Possible explanations :
•Head injury predisposes to both migraine and epilepsy, but
patients with idiopathic epilepsy also have increased risk of
migraine.
•An altered brain state This bi-directional relationship
provides foundation for the use
•Environmental factors of anti-epileptics for migraine
treatment
•Genetic factors
Experience can be defined as
yesterday’s answer to today’s problems
10. Goals
Goals Of treatment
reduce the diminish the shorten the
frequency of severity of duration of
(or eliminate) migraine migraine
migraine attacks attacks
attacks
Prophylaxis is considered successful if the frequency,
duration, and/or intensity of attack is decreased by at
least 50%.
Journal of Pharmacy Practice. 1993; 253-270.
It is the province of the knowledge to speak
and it is the privilege of the wisdomto listen - Hodly’s
11. Measures
Non-pharmacologic
Reduce the patient’s exposure to triggers that may
cause a migraine attack to start.
•missed meals
Patients •too little sleep
should be
encouraged •excessive heat and humidity
to keep a •foods such as chocolate, hard cheeses,
headache alcoholic beverages, citrus fruits, nuts,
diary in an excessive caffeine, and caffeine withdrawal
effort to •medication such as oral contraceptives
identify overuse of analgesics
triggers.
•strong sensory stimuli such as bright lights,
glare,flickering lights, odors, smoke and
prolonged exposure to heat or cold.
The meek shall inherit the earth
- but not its mineral rights
12. Guidelines
Indications for pharmacologic prophylaxis
US Headache Consortium Guidelines
• recurring migraines that, in the patients' opinion,
significantly interfere with their daily routines,
despite acute treatment
• frequent headaches (more than two per week)
• contraindication to adverse events or failure or
overuse of acute therapies
• the use of acute medication more than twice a week
• presence of uncommon migraine conditions
Curr Med Res Opin 17(1s):s87-s93, 2001.
Our best thoughts come from others
13. Therapy
Drug classes for Migraine Prophylaxis
β-blockers
Antidepressants
Calcium channel antagonists
Serotonin antagonists
Anti-epileptics
NSAIDs
Others
(including riboflavin, minerals and herbs)
Curr Med Res Opin 17(1s):s87-s93, 2001
14. Antiepileptics
With newer advances in
knowledge of
co-morbidity with
epilepsy, the new
frontier for migraine
prophylaxis is use of
anti-epileptic drugs.
Family Practice, 2001, Vol. 18, No. 1, 101-106
Success is a prize to be won. Action is the road to it.
Chance is what may lurk in the shadows at the road side.
- O. Henry
15. Principles of rational polypharmacy
• Correctly identify the epilepsy syndrome
• Select the drug that
- is effective for the epilepsy syndrome
- has the least potential for adverse effects of concern to
the patient. E.g. teratogenicity, skin rash, weight gain
- is most economical
• Initiate treatment with one drug
• If seizures are only partially controlled at maximally
tolerated doses, consider polypharmacy
• For the second, select one that has
– A different mechanism of action
– The lowest potential for metabolic interactions
– The lowest potential for adverse effects
It is a great misfortune not to possess sufficient wit to speak well
nor sufficient judgment to keep silent
La Broyers character
16. Principles of rational polypharmacy
• If addition of the second drug completely controls
seizures, consider very slowly withdrawing the
first drug after six months or more of complete
control
• Carefully record seizures
• If two medications do not completely control
seizure
– Reconsider the diagnosis
– Consider surgical options
– Consider using more than two drugs
We possess by nature the factors out of which personality can be made, and to
organize them into effective personal life is every man’s primary responsibility
- Harry Emerson Fosdick
17. Combinations based on drug interactions
Least useful Rationale
Carbamazepine with phenytoin Phenytoin induces carbmazepine
metabolism, leaading to need for
much higher carbamazepine
doses
Phenobarbital with Phenobarbital is a powerful
carbamazepine inducer of CYP 450 system
Phenytoin, valproate Valproate decreases
Valproate with phenobarbital phenobarbital metabolism
Valproate with phenytoin Both complete for protein
binding sites, reducing the value
of total drug level measurement
Mind is the great level of all things;
human thought is the process by which human ends are
ultimately answered - Daniel Webster
18. Combinations based on drug interaction
Least useful Rationale
Felbamate with phenytoin, Many drug – drug interactions
carbamazepine and valproate
Useful
Gabapentine with any drug No drug interaction
Valproate with lamotrigine Valproate inhibits metabolism of
lamotrigine, reducing dose and
cost of treatment with lamotrigine
“ Social Isolation is in itself a pathogenic
Factor for disease production”
19. Combinations based on mechanism of action
Most useful Rationale
Carbamazepine or phenytoin with Widely different mechanisms of
gabapentine, tiagabine, actions
topiramate, felbamate
Least Useful
Carbamazepine and phenytoin Similar mechanisms of actions
Tiagabine, gabapentine and Similar mechanisms of actions
vigabatrin
Knowledge without action is useless;
Action without knowledge is foolish
20. Combinations based on side effects
Possibly useful Rationale
Valproate with felbamate or Felbamate and topiramate have
topiramate been associated with weight loss,
valproate with weight gain
Least useful
Carbamazepine and valproate in Valproate and carbamazepine
women of child bearing potential both may increase risk for spina
bifida; valproate inhibits
metabolism of 10, 11
carbamazepine epoxide, which
may be teratogenic
A bad teacher complains;
A good teacher explains;
The best teacher inspires;
21. “ Social Isolation is in itself a pathogenic
Factor for disease production”
27. Principles of rational polypharmacy
• Correctly identify the epilepsy syndrome
• Select the drug that
- is effective for the epilepsy syndrome
- has the least potential for adverse effects of concern to
the patient. E.g. teratogenicity, skin rash, weight gain
- is most economical
• Initiate treatment with one drug
• If seizures are only partially controlled at maximally
tolerated doses, consider polypharmacy
• For the second, select one that has
– A different mechanism of action
– The lowest potential for metabolic interactions
– The lowest potential for adverse effects
It is a great misfortune not to possess sufficient wit to speak well
nor sufficient judgment to keep silent
La Broyers character
28. Principles of rational polypharmacy
• If addition of the second drug completely controls
seizures, consider very slowly withdrawing the
first drug after six months or more of complete
control
• Carefully record seizures
• If two medications do not completely control
seizure
– Reconsider the diagnosis
– Consider surgical options
– Consider using more than two drugs
We possess by nature the factors out of which personality can be made, and to
organize them into effective personal life is every man’s primary responsibility
- Harry Emerson Fosdick
29. Combinations based on drug interactions
Least useful Rationale
Carbamazepine with phenytoin Phenytoin induces carbmazepine
metabolism, leaading to need for
much higher carbamazepine
doses
Phenobarbital with Phenobarbital is a powerful
carbamazepine inducer of CYP 450 system
Phenytoin, valproate Valproate decreases
Valproate with phenobarbital phenobarbital metabolism
Valproate with phenytoin Both complete for protein
binding sites, reducing the value
of total drug level measurement
Mind is the great level of all things;
human thought is the process by which human ends are
ultimately answered - Daniel Webster
30. Combinations based on drug interaction
Least useful Rationale
Felbamate with phenytoin, Many drug – drug interactions
carbamazepine and valproate
Useful
Gabapentine with any drug No drug interaction
Valproate with lamotrigine Valproate inhibits metabolism of
lamotrigine, reducing dose and
cost of treatment with lamotrigine
“ Social Isolation is in itself a pathogenic
Factor for disease production”
31. Combinations based on mechanism of action
Most useful
Carbamazepine or phenytoin with Widely different mechanisms of
gabapentine, tiagabine,
Knowledge withoutactions is useless;
action
topiramate, felbamate
Action without knowledge is foolish
32. Combinations based on side effects
Possibly useful Rationale
Valproate with felbamate or Felbamate and topiramate have
topiramate been associated with weight loss,
valproate with weight gain
Least useful
Carbamazepine and valproate in Valproate and carbamazepine
women of child bearing potential both may increase risk for spina
bifida; valproate inhibits
metabolism of 10, 11
carbamazepine epoxide, which
may be teratogenic
A bad teacher complains;
A good teacher explains;
The best teacher inspires;
33. Oxcarbazepine
Pharmaco dynamic properties
• MHD
• Cognitive saccadic smooth pursuit affected
but, focused attention and writing speed
stimulated.
Opinion is ultimately determined by the feelings
and not by the intellect
34. In vitro In vivo pharmaco studies
(SAME AS CARBAMAZEPINE)
In vitro
• Suppresses high frequency repetitive fuing of sodium
dependent action potentials in cultured mouse spinal cord
neurons.
• Acts directly on rat corticostriatal terminals to reduce the
release of excitatory amino acids, probably by inhibiting
high voltage-activated Calcium currents
• Inhibits the electrically and chemically induced release of
excitatory amino acids in rat cortical and striatal slices
• Inhibits penicillin-induced epilepty form discharges in rat
hippocampal slices; an effect affected by the addition of
the potassium channel blocker 4-aminopyridine
T T
he ruth is fear and immorality are two of the greatest
inhibitors of Performance to progress
35. In vitro In vivo pharmaco studies
(SAME AS CARBAMAZEPINE)
In vivo
• Marked inhibitory effect in the hippocampal discharge
test in cats, inhibits photomyoclonic seizures in the
baboon and inhibits electrically and chemically induced
seizures in rats.
• Significantly inhibits pilocarpine-induced status
epilepticus, at clinically relevant doses, in rats compared
with control animals(p=0.001)
• Inhibits the tonic phase of metrazol-induced generalised
tonic-clonic seizures in a dose-dependent manner in rats
• Does not suppress the release of excitatory amino acids
elicited by the normal ongoing electrical activity of the
glutamateric and aspartatergic neurons in rats
“Maintaining the right attitude is easier than
regaining the right mental attitude”
36. Pharmacokinetic properties
(BETTER THAN CARBAMAZEPINE)
Parameter Oxcarbazepine MHD
C max(mg/L) 1.05 – 1.74 5.44 – 8.85
t max (h) 1.0 – 2.0 4.0 – 6.6
AUC(mg/L . h) 5.10 – 6.84 80 – 220
Plasma protein binding(%) 60 – 67 37 – 43
Vdss (L) 49
Vdss adjusted for 0.7 – 0.8
bodyweight(L/kg)
t ½ β (h) 1.0 – 2.5 6.5 – 24.3
CLR (L/h) 0.71 – 1.26
Excretion(% of dose) >96% in urine
<4% in faeces
Imagination is more Important than Knowledge
37. Pharmacokinetic …contd
Parent – 2 hours
MHD – 9 hours
Median tmax – 4.5% (3 – 13 hours)
Steady state MHD – 2- 3 days
Linear – 300 – 2400 mg
“You have got to be before you can do and
do before you can have”
38. Pharmacokinetic …contd
Distribution
Volume - 49 litres (40% - bound to protein)
Binding independent of serum concentration
MHD do not bind to alpha1 acid Glycoprotein
We learn by thinking and the quality of the learning outcome
is determined by the quality of our thoughts
R.B. Schmeck
39. Metabolism and excretion
Liver – cytosolic enzyme – MHD
Conjugation with glucuronic acid
4% oxidised to DHD
Excreted by kidney(95% in urine, 4% - feces,
1% unchanged)
“Peace Rules the day where
Reason Rules the mind”
Colling
40. Special populations
• HEPATIC IMPAIRMENT
Mild to moderate hepatic impairment – no change,
severe – not studied
• RENAL IMPAIRMENT
Half life – increased to 19 hours,
dose adjustment mandatory
• PEDIATRIC USE
>8 years = adults
< 8years 30 – 40% lower
Authority can Rarely Survive in the face of doubt’
- R. Lindner
41. Special populations …contd
• GERIATRIC USE
30 – 60% higher than younger volunteers
cause for this is the age related reduction in
Creatinine clearance
• GENDER
Children, adults elderly same
• RACE
No specific studies
“Fools Admire but men of sense approve”
- A. Pope
42. Summary of randomized, double-blind controlled
trials for new antiepileptic medication involving
children with partial seizures*
AED (study) Design Seizure type Control Subjects
Oxcarbazepine Monotherapy Recent-onset Phenytoin children
(Guerreiro et al) seizures
Oxcarbazepine Monotherapy Recent-onset Placebo Adults and
(Sachdeo et al) seizures children
Oxcarbazepine Monotherapy Refractory partial Placebo Adults and
(Schachter et al) seizures children
Oxcarbazepine Conversion to Refractory partial 300 mg Adults and
(Beydoun et al) monotherapy, seizures children
high Vs low
Oxcarbazepine Adjunctive Refractory partial Placebo children
(Glauser et al) therapy seizures
43. Dosage in Adults (above 16 yrs)
Starting Increment Titration Max.dose
dose period
Initiation as 600 mg/day 300 mg/day Till a dose of 2400 mg/day
monotherapy (BID) every 3rd day 1200 mg/day
is reached
Conversion to 600 mg/day 600 mg/day 2-4 weeks 2400 mg/day
monotherapy from weekly
PHT/VAL/CBZ
The concomitant AEDs should be completely withdrawn over 3-6 weeks
From CBZ (in 1.5 time of Immediate - 1200 mg/day
allergic reaction) CBZ discontinuation
of CBZ
Adjunctive 600 mg/day 600 mg/day Till a dose of 1200 mg/day
Therapy weekly 1200 mg/day
is reached
“ Woman needs society demands”
44. Dosage in children (4-16 years)
Initiation: 8-10 mg/kg/day (Not to exceed 600 mg/day
Body weight Targeted dose/day
20 – 29 kg 900 mg
29.1 – 39 kg 1200 mg
> 39 kg 1800 mg
Titration period – Targeted dose can be achieved over
2 weeks
A woman’s desire for revenge outlasts all her other
45. Relative Efficacy and Tolerability - AEDs
Truth comes out of error sooner than that of confusion
46. Odds ratio – Meta analysis – New AEDs
Thought is the labour of the intellect
Reverie is its pleasure
47. Conclusions from controlled
trials and clinical use
• Oxcarbazepine is preferred safe and effective
first-line monotherapy and first-choice drug
for partial seizures due to
– safe mechanism of action
– better tolerability compared with many other
AEDs
– proven safety in more than
250,000 patient-years
NATURE, TIME AND PATIENCE
are the 3 great physicians
48. Conclusions from controlled
trials and clinical use
• Gold standard efficacy in both children and adults
with newly diagnosed and chronic partial epilepsy
• Effective as monotherapy and as adjunctive
therapy
• Limited interactions
• Individual titration
“Motivation is the Spar k that lights
the Fir e of Knowledge and
fuels the engine of A ccomplishment
49. Titration for initial monotherapy
• Start with 150 mg/day
• Increase by 150 mg/day every
2 days until reach target dose of 900-1200 mg/day
• If necessary you can go faster and start with up to
600 mg/day and titrate with weekly increments of
up to 600 mg/day
At twenty the will rules
At thirty the intellect
At forty the Judgment
50. Oxcarbazepine: dosing guidelines
for children >4 years
Increase by maximum of
Start
10 mg/kg/day
8-10 mg/kg/day
(approximately weekly
(2-3 divided doses)
based on response)
Maximum dose:
51 mg/kg/day in double-blind trials
80 mg/kg/day in open-label trials
A (Neurologist’s) life is like a piece of paper on which
everyone who passes by leaves an impression
- Chinese proverb
51. Titration for conversion to monotherapy
• Immediate conversion scheme
– overnight switch from carbamazepine
to oxcarbazepine possible based on clinical experience
• Gradual conversion scheme
– start oxcarbazepine at 150 mg/day, increase every 2
days by 150 mg/day
– withdraw the baseline AEDs gradually by 25% every
week, starting at day 14
– in case of severe baseline tolerability issues start
baseline dose reduction earlier
The Truth is fear and im oralityare two of the greatest
m
inhibitors of Performance to progress
52. Titration of oxcarbazepine
adjunctive treatment
• Start with 150 mg/day
• Increase by 150 mg/day every
2 days until reach target dose of 1200 mg/day
• Consider reducing the dose of the primary AED in
case of side effects or increasing the dose of
oxcarbazepine in case of incomplete seizure control
It is a great misfortune not to possess sufficient wit to speak well
nor sufficient judgment to keep silent
La Broyers character
53. Conclusions from controlled
trials and clinical use
In summary, oxcarbazepine is a
preferred first-line and first-choice
treatment of partial epilepsy
Every discovery contains an irrational element or
4 creative intuition
- Karl Popper
54. In conclusion-
Role of Oxcarbazepine
Partial with or without generalisation
Adults – Monotherapy / Adjunct
Children – Adjunct only > 4 yrs.
Take time to think; it is the source of power
Take time to read; it is the foundation of wisdom
Take time to work; it is the price of success
55. Neuropathic Pain
• It is the result of injury to the pain-
conducting nervous system
• Disordered peripheral or central nerves
• Compression, transection, infiltration,
ischemia, metabolic injury
56. Neuropathic Pain
• Neuropathic pain, in contrast to nociceptive
pain, is described as "burning", "electric",
"tingling", and "shooting" in nature
• It can be continuous or paroxysmal in
presentation
57. Neuropathic Pain
• Prevalence
– General population 0.6-1%
• Causes
– Compression/infilitration of nerves by:
• Tumors
• Nerve Trauma secondary to procedures
• Nervous System Injury
58. The Pathophysiology
Knowledge about the pathogenesis of
neuropathic pain has grown significantly
over the last 2 decades
59. Anatomy of Nociception
• What is nociception?
– Activation of transduction in nerves that convey
information about tissue damage to the CNS
• Four Steps
1. Transduction
2. Transmission
3. Modulation
4. Perception
60. Pathophysiology
• The hallmarks of neuropathic pain are
chronic allodynia and hyperalgesia
• Allodynia is defined as pain resulting from a
stimulus that ordinarily does not elicit a
painful response (e.g. light touch)
61. Hyperalgesia
• Hyperalgesia is defined as an increased sensitivity
to a normally painful stimuli
• Primary hyperalgesia, caused by sensitization of C–
fibers, occurs immediately within the area of the
injury
• Secondary hyperalgesia, caused by sensitization of
dorsal horn neurons, occurs in the undamaged area
surrounding the injury
62. The allodynia and hyperalgesia associated with
neuropathic pain may be best explained by:
1) The development of spontaneous activity of afferent
input
2) The sprouting of large primary efferents (eg. A–beta
fibers from lamina 3 into lamina 1 and 2)
3) Sprouting of sympathetic efferents into neuromas
and dorsal root and ganglion cells
4) Elimination of intrinsic modulatory systems
5) Up regulation of receptors in the dorsal horn which
mediate excitatory processes
63. The Prerequisite
• For neuropathic pain to manifest clinically, there is
one prerequisite – Classical thermonociceptive
pathways [Peripheral small sensory nerves or ST
Tract & it’s cerebral projections] have to be affected
by the nervous system disease
Casey K, Raven press, 1991; 1-11
Drugs 2000, 60(5); 1029-52
64. Pathophysiology
• Any insult to the nervous system leads to
changes in its structure and function as a result
of reparative processes
• This state of altered properties of the nervous
system is termed neuroplasticity
• In patients with neuropathic pain, neuroplasticity
takes the form of peripheral & central
sensitization, and the main characteristic is
hyperexitability
Drugs 2000, 60(5); 1029-52
66. Altered peripheral afferent function in
inflammatory and neuropathic pain
SympGgl
DRG
TTXr VGCC
VR1, VRL1, SNS/NaN N-type CC
B1,B2, ASIC3, SNS/PN3
P2X3,
TNFαR1, SP
CGRP
67. Injury produces multiple changes in sensory
neurons – increased afferent activity and
secondary central effects
- Transmitters (SP, CGRP)
- Receptor (VR1, P2X3)
- Ion channels (TTXs, TTXr)
- Physiology (↓ Cond Veloc)
- Anatomy (? Cell death, basketing)
SKIN
CNS
DRG
Transganglionic
↓ Retrograde transport degeneration
of trophic factors Central sprouting of A-
fibres
↓ Opioid receptors
68. Kivun kr Assessment of Chronic
Pain using fMRI
Physiological pain Pathological pain
(pre capsaicin, 48°C) (post capsaicin, 43°C)
Note enhanced parietal (somatosensory association) and frontal (attention)
lobe activity in the capsaicin induced thermal hyperalgesia model (right)
69. Neuropathic Pain & Epilepsy
• There is notable similarity between the
patho-physiological and biochemical
mechanisms observed in epilepsy and
neuropathic pain
J Am Geriartr Soc 1995; 43: 1279-89
70. Examples of Neuropathic Pain
• Trigeminal Neuralgia
• Diabetic & Other painful polyneuropathies
• PHN
• Trauma to major nerve trunks
• Cancer related
• Spinal cord disorders like multiple sclerosis and
injuries
• Brainstem & hemispheric injuries and Strokes
71. DIABETES MELLITUS
• 1990 – 2000 – Decade of brain.
• 2001-2010 - Decade of pain control & research
• India – Diabetic capital of the world.
• Every fifth Indian will be a diabetic.
• Every fifth diabetic in the world will be an Indian.
• 32 million diabetics at present.
• 250% rise by 2035 – 100 million
72. Risk factors
For Painful neuropathy For painless neuropathy
• Hyperglycemia • Greater height
• Hypertension • Male gender
• Dysmetabolic syndrome • Smoking
HT+DM+IHD+DYSLIPIDEMIA • Total abstinence from
alcohol
• High HbA1C
When they tell you to grow up, they mean stop growing
73. Diabetic polyneuropathy
• The most common type of diabetic
neuropathy.
• Presents primarily with sensory symptoms
& pain
• May have a prominent autonomic
component.
• Associated with secondary complications
of neuropathy
Of a burning and unremitting character - F.W.PAVY
74. Prevalence of Polyneuropathy
(Variable depending on criteria)
All patients Type 1 Type 2
with
polyneuropathy
Symtomatic 54% 45%
plyneuropathy
Neuropathy 15% 13%
impairment
scale.+ 7 (Rochester
abnormal tests study)
76. Types of painful neuropathies
Acute (< 6 months) Chronic(> 6 months)
• Truncal neuropathy. • Distal symmetrical painful
• cachectic neuropathy-Acute, sensorimotor
painful,wt.loss,poor control of polyneuropathy
DM
• Entrapment neuropathies
• Insulin neuritis -Acute painful,
weight loss, good control of • Difficult to treat.
DM
• Painful 3rd cranial nerve palsy.
• Easy to treat.
Speak obligingly even if you cannot oblige
77. Pathogenesis
1.Metabolic
2.Vascular -reduced endoneural blood flow
and nerve ischemia
3.Oxidative stress
4.Autoimmune
5.Neurohormonal growth factor deficiency
Knowledge without action is useless;
Action without knowledge is foolish
78. Oxidative stress
Hyperglycemia ↑ NO
↑Aldose reductase activity
3 Anti phospholpid antibody
Ab to gangliosides.
1
GLA deficiency 4
Nerve damage
5
↓PGI2,PG Nerve growth factor
deficiency
2
Protein kinase C deficiency
Microvasculopathy
79. Pain Vs nociception
• Pain is a subjective phenomena, expression
depends on the emotional experience.
• Both central & peripheral mechanisms are
involved.
• Link between neural function and the
subjective experience.
A bad teacher complains;
A good teacher explains;
The best teacher inspires;
82. Generation of pain
• Central terminals of unmyelinated primary c-
afferents project to dorsal horn and make
contact with secondary pain signaling neurons.
• A-beta afferents project without synaptic
transmission into dorsal columns and also
contact dorsal horn neurons.
I don’t like peripheral neuritis– it interferes with work
83. Generation of pain
• The hallmark of neuropathic pain is chronic
allodynia & hyperalgesia.
• C-fiber sensitization produces primary hyperalgesia
– from immediately within the area of injury.
• Sensitization of DRG produces secondary
hyperalgesia – from undamaged area surrounding
the injury
Teachers are reservoirs from which, through the process of education,
the students draw the water of life
84. Generation of pain
• The hallmark of neuropathic pain is chronic
allodynia & hyperalgesia.
• C-fiber sensitization produces primary hyperalgesia
– from immediately within the area of injury.
• Sensitization of DRG produces secondary
hyperalgesia – from undamaged area surrounding
the injury
It is not your position that makes you happy or unhappy
It is your disposition
85. Clinical features –
Distal symmetrical painful
sensorimotor polyneuropathy
• Burning, superficial pain. Hypoalgesia in later
stages.
• Defective thermal sensation.
• Impaired vasomotion
• Defective autonomic function
• Intact DTR and power till late stages.
• Progressive with increasing duration of diabetes.
• Related to glycemic control & complications.
86. Clinical features –
Truncal neuropathy
• Truncal polyneuropathy • Truncal radiculopathy
• Rare • Acute onset of pain in a
• Occur in long standing DM radicular pattern
• “Bandlike” Painful symptoms • Asymmetrical pain
in thoracic root distribution • Patchy sensory loss is a
• Motor involvement- muscle clue to the diagnosis.
herniation – asymmetric bulge
in abdominal wall
Learn to adapt, adjust and accommodate
Learn to give, not to take and learn to serve not to rule
87. Clinical features Insulin neuritis
• Acute painful, occurs 1 month after insulin /OHA.
• Due to rapid glycemic control.
• Nerves in these patients are under general hypoxia
and use glucose under anaerobic conditions.
• Once glucose is normalised in blood and nerves,
glucose is no longer available and the nerves
undergo degeneration.
Reputation is made in a moment; character is built in a life time
88. Insulin neuritis- contd..,
• Burning pain, paraesthesia, allodynia with
nocturnal exacerbation.
• Depression is a feature.
• No weight loss.
• Sensory loss is mild. No motor signs.
• Complete resolution in 1 year.
A good teacher is a perpetual learner
89. Clinical features - Cachectic neuropathy
• In patients with a poor control of DM.
• Wt.loss is prominent.
• Severe burning pain- continuous or intermittent.
• Subjective feeling of swollen limb.
• Allodynia is common- nocturnal exacerbation.
• Sensory loss is mild.
• No motor signs.
T T
he ruth is fear and immorality are two of the greatest
inhibitors of Performance to progress
90. Differntial diagnosis
• Claudication
• Radiculopathy
• Charcoat’s neuroarthropathy
• Plantar fasciitis
• Tarsal tunnel syndrome
• Osteoarthritis
A great many people think they are thinking when they
are merely re arranging their prejudices
W. James
96. READ not to contradict or confute
Nor to Believe and Take for Granted
but TO WEIGH AND CONSIDER
THANK YOU
My sincere thanks to G. Kakuthan for his
meticulous computer work