Isolated Elevated Homocysteine

Induced Peripheral Neuropathy

F I T R I O C TAV I A N A

C L I N I C A L N E U R O P H Y S I O L O G Y D I V I S I O N - N E U R O L O G Y D E PA RT M E N T

FA C U LT Y O F M E D I C I N E U N I V E R S I TA S I N D O N E S I A /

D R . C I P T O M A N G U N K U S U M O H O S P I TA L
Outline
Introduction
Clinical Approach of Neuropathy
Isolated Elevated Homocysteine Induced Peripheral Neuropathy
 Introduction
Peripheral neuropathy refers to disorders of the peripheral nervous system which may be caused either
by diseases of the nerve or from the side effect of the systemic illness

The overall prevalence of peripheral neuropathy is 2.4%, increases to 8% in individuals aged above 55
years

Misra UK, et al. Ann Indian Acad Neurol 2008;11(2):89-97

 History

Symptoms and Topography

Clinical Examination
Approach
Electrodiagnostic Evaluation

Laboratory test
History
Acute
• <4 weeks

Sub-acute
• 4-12 weeks

Chronic
• > 12 weeks
 Sensory

• Positive: burning, pain, walking on cotton wool,

band-like sensation on feet or trunk, tingling, pins and
needles
• Negative : numbness, loss of sensation

History Motor

• Weakness

Autonomic

• Postural hypotension, impotence, sphincter

disturbance, diarrhea, constipation, dryness or
excessive sweating point
Symptom and Topography
Location
◦ Unilateral / Bilateral
◦ Distal/ Proximal predominance
◦ Mononeuropathy / mononeuropathy multiplex / polyneuropathy

Sensory Involvement
◦ Pain, loss of temperature sensation and autonomic symptoms  small fiber
◦ Ataxia in the dark  large fiber
Neuropathy
Pattern
Nerve fibers
in peripheral
neuropathy
 Muscle Power

Tendon Reflexes

• Distal reflex loss (in length-dependent

axonopathies)
Examination • Generalized reflex loss (in acquired demyelinating
neuropathies)

Sensory examination

• Vibration and joint position : large fiber

• Pin-prick, pain and temperature: small fiber
Electrodiagnostic Evaluation
Motor and Sensory
Nerve conduction study Axonal / Demyelination
Conduction Block

F-wave
Late response H-reflex

Neurogenic Changes
EMG Spontaneous activity
Laboratory Test
First line screening test for neuropathy
◦ Blood count, ESR
◦ Blood sugar
◦ Liver and renal function tests
◦ Serum vitamin B12
◦ Thyroid function test
◦ Vasculitis profile
◦ Paraprotein
 Drug and Toxin: Alcohol, vincristine, phenytoins, statins

Infection: leprosy, HIV

Connective tissues: Sjogren’s syndrome, SLE, RA

Metabolic: diabetes, chronic renal failure

Chronic Axonal Paraneoplastic

Neuropathies
Inherited

Vitamin Deficiency: B12, Folic acid, vitamin E

Endocrine: Hypohyroidism

Paraproteinemia: Myxedema, Waldenstorm’s disease, Benign monoclonal

gammopathy
 Clinical
Approach

England JD, et al. Lancet 2004;363:2151-61

Hyper-
homocysteine and
Polyneuropathy
Shandal V, et al. J Clin Neuromusc Dis. 2016;17:106-9
Shandal V, et al. J Clin Neuromusc Dis. 2016;17:106-9
The electrophysiologic features are a mild large fibre sensorimotor neuropathy with mild
demyelination and distal axonal degeneration
Luo JJ, et al. J Neurol Transl Neurosci 2013;2(1): 1027
Hsu RT, et al. J Neurol Exp Neurosci.2020;6(2):58-61
 Hcy levels increases when:

• vitamin B12/folate deficiency that affects re-

methylation pathway,

• vitamin B6 deficiency or cystathionine beta-

synthase dysfunction that controls the trans-
sulfuration of Hcy to cystathionine, or

• methylenetetrahydrofolate reductase gene

mutation.
 eHcy

Overstimulating NMDA receptors

Inducing Calcium influx

Excitotoxic and oxidative stress

Neuronal Death/ Apoptosis & Endothelial Cell Injury

Diaz-Arrastia R. Arch Neurol.2000;57:1422-28

Wile DJ, et al. Diabetes Care, 2010:33:156-61
eHcy and Neurologic Disorders
Stroke
Mild cognitive impairment
Dementia
Parkinson’s Disease
Multiple Sclerosis
Epilepsy
Peripheral Neuropathy
Take Home Messages
Clinical approach in diagnosis of polyneuropathy includes taking history thoroughly, physical
examination, electrodiagnosis evaluation and laboratory test.

Isolated elevated of Homocysteine (eHcy) should be considered as etiology of polyneuropathy

eHcy in Diabetic patients could worsen the diabetic polyneuropathy

Polyneuropathy due to eHcy is a treatable neurologic disorder

Thank You