بالحضور بالحضور مرحبا مرحباالكرامالكرام

الرحيم الرحمن الله الرحيم بسم الرحمن الله بسم

وما أوتيتم من ألعلم إال وما أوتيتم من ألعلم إال •قليالقليال

صدق الله العظيمصدق الله العظيم•

Peripheral Peripheral Neuropathy InNeuropathy InDyslipidemia Dyslipidemia with special with special Emphasis on Emphasis on

diabetes diabetes mellitus mellitus (Biochemical & (Biochemical &

Electrophysiological study)Electrophysiological study)

Peripheral neuropathyPeripheral neuropathy

• DefDef: PNP is a generic term for : PNP is a generic term for

peripheral nerve disorders of any cause. peripheral nerve disorders of any cause.

• Mononeuropathy refers to involvement Mononeuropathy refers to involvement

of a single nerve whereas of a single nerve whereas

polyneuropathy refers to involvement of polyneuropathy refers to involvement of

multiple nerves.multiple nerves.

1.1. dyslipidemia could be associated with subclinical dyslipidemia could be associated with subclinical peripheral neuropathy, which may occur more peripheral neuropathy, which may occur more frequently in patients with very high mean serum frequently in patients with very high mean serum level of T.G, T.C and LDL.level of T.G, T.C and LDL.

2.2. The type of peripheral neuropathy that occurs in The type of peripheral neuropathy that occurs in Dyslipidemia is mainly a sensory type, although Dyslipidemia is mainly a sensory type, although motor neuropathy can not be excluded.motor neuropathy can not be excluded.

3. The underlying mechanism is mixed axonal 3. The underlying mechanism is mixed axonal degeneration and segmental demyelination; degeneration and segmental demyelination; however, the demyelination is thought to be however, the demyelination is thought to be secondary to the axonal degeneration. The secondary to the axonal degeneration. The peripheral neuropathy associated with peripheral neuropathy associated with dyslipidemia is symmetrical type.dyslipidemia is symmetrical type.

PNP in DyslipidemiaPNP in Dyslipidemia

Pathogenesis of Pathogenesis of PeripheralPeripheral Neuropathy inNeuropathy in

Dyslipidemia DyslipidemiaI.I. Involvement of structural lipidsInvolvement of structural lipids

II.II. The action of lipoproteins as The action of lipoproteins as enzyme co-factor and as a enzyme co-factor and as a bound intermediate in the bound intermediate in the biosynthesis of polysaccharides biosynthesis of polysaccharides and proteins.and proteins.

III.III. Nerve infarction which is Nerve infarction which is mediated via fat embolism or mediated via fat embolism or lipid induced platelet lipid induced platelet aggregation.aggregation.

Types of peripheral Types of peripheral neuropathy in DMneuropathy in DM

• PNP affect 30% of diabetic patients.PNP affect 30% of diabetic patients.

• Diabetic neuropathy divided into:Diabetic neuropathy divided into:

A.A.somaticsomatic: include:: include:

1. polyneuropathy 1. polyneuropathy symmetrical symmetrical

(mainly sensory and (mainly sensory and distal)distal)

Asymmetrical Asymmetrical (mainly(mainly

motor and motor and proximal)proximal)

2. Mononeuropathy (including mononeuritis2. Mononeuropathy (including mononeuritis

multiplex)multiplex)

B. B. VisceralVisceral (autonomic) (autonomic)

Pathogenesis of Pathogenesis of peripheral neuropathy in peripheral neuropathy in

DMDMThe pathogenesis of sensorimotor

neuropathy in D.M is multifactorial

and related metabolic disturbances,

such as hyperglycemia, dyslipidemia,

oxidative stress and growth factor

deficiency all contribute to the

development of this complication.

Several metabolic products, such

as:

1.Advanced glycated end products.

2. Activation of protein kinase C

enzyme.

3.Sorbitol aldose reductase (polyol)

pathway flux, are claimed to have a

role in pathogenesis of neuropathy

Dyslipidemia as a contributory factor in etiopathogenesis of diabetic

neuropathy

Dyslipidemia leads to high levels of oxLDLs Dyslipidemia leads to high levels of oxLDLs that may injure DRG neurons via LOX-1 that may injure DRG neurons via LOX-1 receptor and contribute to the development of receptor and contribute to the development of diabetic neuropathy.diabetic neuropathy.

Also these oxLDLs that carry lipids to the Also these oxLDLs that carry lipids to the periphery could be one factor that acts in periphery could be one factor that acts in concert with glucose to increase sensory nerve concert with glucose to increase sensory nerve injury. injury.

These same mechanisms also occur in These same mechanisms also occur in

the blood microvessels, leading to the blood microvessels, leading to

multiple neurovascular targets for multiple neurovascular targets for

oxidative stress mediated injury.oxidative stress mediated injury.

Neurological complications of dyslipidemia were Neurological complications of dyslipidemia were firstly noticed in hereditary lipid disorders like firstly noticed in hereditary lipid disorders like Tangier disease, abetalipoprotienemia, later on Tangier disease, abetalipoprotienemia, later on many studies was carried out to disclose the many studies was carried out to disclose the relation between peripheral neuropathy and relation between peripheral neuropathy and dyslipidemia, but in spite of all these studies the dyslipidemia, but in spite of all these studies the proportion of dyslipidemic patients with peripheral proportion of dyslipidemic patients with peripheral neuropathy is still unknown and based on neuropathy is still unknown and based on literature review.literature review.

Role of Electrophysiology in DyslipidemiaRole of Electrophysiology in DyslipidemiaRole of Electrophysiology in DyslipidemiaRole of Electrophysiology in Dyslipidemia

ELECTROPHYSIOLOGICAL ASSESSMENT ELECTROPHYSIOLOGICAL ASSESSMENT OF THE PERIPHERAL NERVOUS OF THE PERIPHERAL NERVOUS SYSTEM:-SYSTEM:-

Electrophysiological methods have made an important contribution in elucidating the pathophysiology of peripheral nerve disorders by ELECTRONEUROGRAPHY which include:-

A. SENSORY NERVE CONDUCTION. B. MOTOR NERVE CONDUCTION.

C. F -WAVE CONDUCTION STUDY.

PARAMETER

Subject NO.

Rt. Median N.Mean ±S.D

Rt. Ulnar N.Mean ± S.D

Rt.Com.Per. N.Mean ± S.D

Rt. Post.Tib. N.Mean ± S.D

DSL (msec)

Patients 68 2.65 ± 0.58 2.44 ± 0.50 3.52± 0.88 3.60± 0.96

Control 42 2.44 ± 0.17 2.29 ± 0.16 3.05 ± 0.22 3.12 ± 0.27

P.value (S) (N.S) (H.S) (H.S)

Amplitude (µv)

Patients 68 22.63 ±5.56 20.75±3.69 9.65± 2.97 9.92± 3.75

Control 42 25.25 ±2.24 22.04 ±1.71 11.07 ±1.37 11.66 ±1.81

P.value (H.S) (S) (H.S) (H.S)

C.V (m/sec)

Patients 68 57.34 ±7.12 57.55 ±6.77 47.70±8.19 47.88±8.01

Control 42 59.67 ±3.07 59.41 ±3.44 51.48 ±4.55 51.61 ±3.97

P.value (S) (N.S) (H.S) (H.S)

Patients with Abnormal Patients with Abnormal Electrophysiologic ResultsElectrophysiologic Results

PARAMETER

SUBJECT NO.

Rt.Median N.Mean ± S.D

Rt.Ulnar N.Mean ± S.D

Rt.Com. Per. N Mean ±S.D

Rt.Post. Tib. N.Mean ± S.D

DSL (msec)

Control 42 2.44 ± 0.17 2.29 ± 0.16 3.05± 0.22 3.12 ± 0.27

Affected 21 3.11 ± 0.84 2.79 ± 0.75 4.39 ± 1.06 4.73 ± 0.96

P.value (H.S) (H.S) (H.S) (H.S)

AMPLITUDE (µv)

Control 42 25.25 ±2.24 22.04±1.71 11.07 ±1.37 11.66 ±1.81

Affected 21 18.25 ±5.87 17.76±4.92 6.62 ± 3.23 5.96 ± 3.46

P.value (H.S) (H.S) (H.S) (H.S)

C.V (m/sec)

Control 42 59.67 ±3.07 59.4 ±3.44 51.48 ±4.55 51.61 ±3.97

Affected 21 51.45 ±9.58 54.0 ±8.56 39.19 ±7.25 38.85 ±6.91

P.value (H.S) (H.S) (H.S) (H.S)

RecommendationsRecommendations Dyslipidemia is a causative factor for peripheral Dyslipidemia is a causative factor for peripheral

neuropathy, which stresses the importance of screening neuropathy, which stresses the importance of screening

patients with peripheral neuropathy of unknown origin for patients with peripheral neuropathy of unknown origin for

dyslipidemia, as it is a potentially treatable condition.dyslipidemia, as it is a potentially treatable condition.

Electrophysiologically, we recommend to examine the Electrophysiologically, we recommend to examine the

patients, at first, for nerves of lower limbs, as they are patients, at first, for nerves of lower limbs, as they are

usually the first to be affected. Starting with sensory fibers usually the first to be affected. Starting with sensory fibers

assessment and further tests are done according to these assessment and further tests are done according to these

findings. findings.

Unilateral sensory nerve conduction study will Unilateral sensory nerve conduction study will

be reasonably informative since the disease be reasonably informative since the disease

process found to affect both sides of the body process found to affect both sides of the body

equally. Examination of upper limbs mainly equally. Examination of upper limbs mainly

median nerve sensory conduction study will be median nerve sensory conduction study will be

supportive and helpful to see the degree of supportive and helpful to see the degree of

extension of the disease process.extension of the disease process.

Motor nerve conduction study Motor nerve conduction study

could be helpful and informative could be helpful and informative

if the patients have abnormal if the patients have abnormal

sensory nerve conduction study. sensory nerve conduction study.

So further evaluation of patients So further evaluation of patients

by MNCS and F-wave conduction by MNCS and F-wave conduction

study is recommended. study is recommended.

Thank youThank you