types of neuropathy classification and management

1. Dr. Anoop.K.R
Dept of General Medicine

2.  Generalized term including disorders of any
cause affecting PNS
 May involve sensory nerves, motor nerves, or
both
 May affect one nerve (mononeuropathy),
several nerves together (polyneuropathy) or
several nerves not contiguous
(Mononeuropathy multiplex)

3.  Further classified into those that primarily
affect the cell body (e.g., neuronopathy or
ganglionopathy), myelin (myelinopathy), and
the axon (axonopathy)

4.  Disease
 Diabetes1 2
 Paraproteinaemia2 3
 Alcohol misuse1
 Renal failure1
 Vitamin B-12 deficiency1
 HIV infection1
 Chronic idiopathic
axonal neuropathy4
 Prevalence
 11-41% (depending on
duration, type,and
control)
 9-10%
 7%
 4%
 3.6%
 16% (depending on the
population studied,
usually much lower)
 10-40% of different
hospital series
BMJ 2010:341:c6100

5. Loss of function
“- symptoms”
Disordered function
“+ symptoms”
Sensory
“Large Fiber”
↓ Vibration
↓ Proprioception
Hyporeflexia
Sensory ataxia
Paresthesias
Sensory
“Small Fiber”
↓ Pain
↓ Temperature
Dysesthesias
Allodynia
The clinical response to sensory nerve injury

6. Loss of function
“- symptoms”
Disturbed function
“+ symptoms”
Motor nerves
Large fibre
Wasting
Hypotonia
Weakness
Hyporeflexia
Orthopedic deformity
Fasciculation
Cramps
The clinical response to motor nerve injury

7. Loss of function
“- symptoms”
Disturbed function
“+ symptoms”
Autonomic nerves ↓ Sweating
Hypotension
Urinary retention
Impotence
Vascular color changes
↑ Sweating
Hypertension
The clinical response to autonomic nerve injury

9.  By far the majority of the toxic, metabolic and
endocrine causes
 NCVs: CMAPs ↓ 80% lower limit of normal w/o or
min velocity or distal motor latency change.
 Legs>> arms.
 EMG: Signs of denervation (acute, chronic) and
reinnervation

10.  Unusual by comparison with axonopathies
 Clues: hypertrophic nerves on exam
global arreflexia
weakness without wasting
motor >> sensory deficits
NCS can discriminate inherited from
acquired
 NCS: Distal motor latency prolonged (>125%
ULN)
Conduction velocities slowed (<80% LLN)
May have conduction block
EMG: Reduced recruitment w/o much
denervation

11.  SJOGREN’S SYNDROME
 VIT B12 NEUROPATHY
 CISPLATIN
 PYRIDOXINE NEUROTOXICITY
 FRIEDEREICH’S ATAXIA

12. PAIN-
burning,shock
like,stabbing,pric
kling,shooting,la
ncinating
Allodynia
Decreased
pinprick
sensation
Tight band like
pressure
Insensitive to
heat and cold
Diminished
temperature
sensation

13.  Heriditary sensory neuropathy
 Lepromatous leprosy
 Diabetes mellitus
 Amyloidosis(early familial&primary)
 Tangier disease
 Fabry’s disease-pain predomonates
 Dysautonomia-riley-day syndrome
 HIV & antiretroviral therapy neuropathy

14.  Global sensory loss
 Carcinomatous sensory neuropathy
 Hereditary sensory neuropathy
 Diabetic sensory neuropathy
 Vacor intoxication
 Xanthomatous neuropathy of primary biliary
cirrhosis

15.  Immune neuropathies
 Heriditary motor sensory neuropathies
 Acute intermittent porphyria
 Diphtheritic neuropathy
 Lead neuropathy
 Brachial neuritis
 Diabetic lumbosacralplexus neuropathy

16.  Acute-pandysautonomia
 -botulism
 -porphyria
 -GBS
 -Amiodarone
 -vincristine
 Chronic-amyloid,diabetes,sjogren’s,HSN
1&3,chagas,paraneoplastic

17.  ?MONONEUROPATH
Y
 Focal involvement
of a single nerve
 Weakness &
sensory loss in the
territory of a single
peripheral nerve
 Pain along the
pathway of the
nerve
Direct
trauma
compressio
n
entrapment Vascular
lesions
neoplasms

18.  Random pattern of nerve involvement
 In distribution of separate
nerves,asymmetric
 May/may not be painful
 Not length dependent
 Isolated reflex loss
 CAUSES—inflammatory-leprosy,sarcoid
 Vascular-Diabetes
 Pressure,Trauma,Infiltration
 Vasculitis-
PAN,SLE,RA,scleroderma
 Immune-vaccination

19.  MC type –Distal symmetric polyneurpathy
 Burning sensation,tingling,numbness
 Length dependent pattern
 Starts in feet,distal stocking glove pattern
 Fairly symmetric
 Symmetrically decreased reflexes
 Sensory>motor

20.  Diabetes mellitus
 Alcohol
 Vit B12 deficiency
 HIV
 Although more than
 one nerve involved
 one will be prominant

21.  Lumbosacral polyradiculopathy/stenosis
 Myelopathy-structural
 -nonstructural
 Vascular insufficiency-exercise related
cramps,aching pain>numbness
 Orthopedics –stress #,plantar fascitis

22.  ?POLYRADICULOPATHY
 Disease of multiple peripheral nerve roots
 Asymmetric with erratic distribution-proximal in
one,distal in another
 Pain is a common feature
 ?MONORADICULOPATHY
 Root disease by disease of spinal column
 Changes in distribution of spinal nerve root

23.  ?SENSORY NEURONOPATHY
 Ganglion cells predominantly affected
 Both proximal & distal involvement
 Sensory ataxia is common
 No weakness
 But awkward movement d/t sensory disturbances
 ?MOTOR NEURONOPATHY
 Disorder of ant horn cells
 Weakness,fasciculation,atrophy
 Not properly a process of peripheral NP

24.  ?PLEXOPATHY
 Asymmetric
 Painful onset
 Multiple nerves in a single limb
 Rapid onset of weakness,atrophy
 Isolated reflex loss

25.  a/c idiopathic polyneuritis
 Peripheral nerve+cranial nerve involvement
 Self limiting painful ophthalmoplegia
 CAUSES-TB meningitis
 osteomyelitis skull
 otitis media
 syphilitic meningitis
 sarcoidosis
 carcinomatous meningitis

26. 1.syndrome of a/c ascending motor paralysis
a.acute idiopathic polyneuritis
b.IMN with polyneuritis
c.diphtheria
d.hepatitis with polyneuritis
e.porphyria
f.TOCP poisoning
g.paraneoplastic
h.post vaccinial

27. 2.syndome of subacute sensorymotor NP
A.Deficiency=alcoholic beriberi
pellagra
vit B12
B.Toxins=arsenic,lead,Hg,Pb
C.Drugs=nitrofurantoin,INH
dapsone,disulfiram
clioquinol
D.Uremic
E.DM,PAN,sarcoidosis
A,B,C,D====SYMMETRIC

28. 3.C/C sensorimotor polyneuropathy syndrome
GENETIC ACQUIRED
Peronealmuscle atrophy/CMT leprosy
Dejerine sottas disease Diabetes mellitus
Hereditary sensory NP uremia
Portugeseamyloidosis/
andrade’s disease
carcinoma
Refsum’s disease myeloma
A beta lipoproteinemia paraproteinemia
Tangier’s disease amyloidosis
Metachromaticleucodystrophy

29.  RECURRENT POLYNEUROPATHY
 Relapsing CIDP
 Porphyria
 Refsum’s disease
 HNPP
 GBS
 Beriberi
 Toxic neuropathy

30.  SENSORY ATAXIC NEUROPATHY
 Sensory NP(polyganglionopathy)
 Paraneoplastic sensory NP=sjogren’s
 =idiopathic
 Toxic=cisplatin
 =vit B6 excess
 Demyelinating polyradiculopathy=MGUS
 =Millerfisher

32.  DM
 hypothyroidism
 chronic renal failure
 liver disease
 intestinal
malabsorption
 malignancy
 connective tissue
diseases
 [HIV]
 drug use
 Vitamin B6 toxicity
 alcohol and dietary
habits
•Weight loss, malaise, and anorexia.

33.  Diabetes and Pre-Diabetes
 Alcohol neuropathy
 Chemotherapy
◦ Platinum-based
 Paraproteinemia
 Vasculitis and Connective Tissue Diseases
 Heavy metals and other toxins
 HIV
 Amyloidosis
 Porphyria

34.  Axonal
Vincristine
Paclitaxel
Nitrous oxide
Colchicine Probenecid
Isoniazid
Hydralazine
Metronidazole
Pyridoxine
Didanosine
Lithium
Alfa interferon
Dapsone
 Axonal - continued..
Phenytoin
Cimetidine
Disulfiram
Chloroquine
Ethambutol
Amitriptyline
 Demyelinating
Amiodarone
Chloroquine
Suramin
Gold
 Neuronopathy
Thalidomide
Cisplatin
Pyridoxine

35.  ETIOLOGICAL CLASSIFICATION
 1.metabolic-DM,amyloidosis,porphyria
 2.infections-leprosy,HIV,CMV,syphilis,
 diphtheria,lymedisease
 3.immune- GBS,CIDN,MMN
 4.hereditary-CMT
 5.Toxic-drugs,alcohol,heavymetals
 6.vasculitis-PAN,CSS,cryoglobulinemia
 7.paraneoplastic-lung
 8.nutritional- B1,B6,B12

36. ◦ Guillain-Barré syndrome
◦ Chronic inflammatory demyelinating
polyradiculoneuropathy
◦ Diabetes mellitus
◦ Porphyria
◦ Osteosclerotic myeloma
◦ Waldenstrom's macroglobulinemia
◦ Monoclonal gammopathy of undetermined significance
◦ Acute arsenic polyneuropathy
◦ Lymphoma
◦ Diphtheria
◦ HIV/AIDS
◦ Lyme disease
◦ Hypothyroidism
◦ Vincristine (Oncovin, Vincosar PFS) toxicity

37.  The temporal course of a neuropathy varies,
based on the etiology.
◦ With trauma or ischemic infarction, the onset will
be acute, with the most severe symptoms at
onset.
◦ Inflammatory and some metabolic neuropathies
have a subacute course extending over days to
weeks.
◦ A chronic course over weeks to months is the
hallmark of most toxic and metabolic
neuropathies.

38.  A chronic, slowly progressive neuropathy over
many years occurs with most hereditary
neuropathies or with chronic inflammatory
demyelinating polyradiculoneuropathy (CIDP).
 Neuropathies with a relapsing and remitting
course include CIDP, acute porphyria,
Refsum's disease, hereditary neuropathy with
liability to pressure palsies (HNPP), familial
brachial plexus neuropathy, and repeated
episodes of toxin exposure.

39.  Ischemic neuropathies often have pain as a
prominent feature.
 Small-fiber neuropathies often present with
burning pain, lightning-like or lancinating
pain, aching, or uncomfortable paresthesias
(dysesthesias).

40.  Dying-back (distal symmetric axonal)
neuropathies initially involve the tips of the
toes and progress proximally in a stocking-
glove distribution.

41.  Peripheral neuropathy can present as restless
leg syndrome.
 Proximal involvement may result in difficulty
climbing stairs, getting out of a chair, lifting
and bulbar involvement can also be seen

42.  The clinical assessment should include:
◦ careful past medical history, looking for systemic
diseases that can be associated with neuropathy,
such as diabetes or hypothyroidism.

43.  All patients should be questioned regarding
◦ HIV risk factors
◦ diet (nutrition)
◦ vitamin use (especially B6)
◦ possibility of a tick bite (Lyme disease)
◦ Constitutional symtoms (malignancy)

44. Acute onset
(within days)
Subacute onset
(weeks to months)
Chronic
course/
insidious
onset
Relapsing/
remitting
course
Guillain-Barré
syndrome
Maintained exposure to
toxic
agents/medications
Hereditary motor
sensory
neuropathies
Guillain-Barré
syndrome
Acute intermittent
porphyria
Persisting nutritional
deficiency
Dominantly
inherited sensory
neuropathy
CIDP
Critical illness
polyneuropathy
Abnormal metabolic
state
CIDP HIV/AIDS
Diphtheric
neuropathy
Paraneoplastic
syndrome
Toxic
Thallium toxicity CIDP Porphyria

45.  A cranial nerve examination can provide
evidence of mononeuropathies.
 Funduscopic examination may show
abnormalities such as optic pallor, which can
be present in leukodystrophies and vitamin
B12 deficiency.

46.  Thickened nerves

47.  Cardiovagal
◦ Heart rate variability
 Adrenergic
◦ Valsalva maneuver
 Induces BP changes and monitors pulse reaction
 Postganglionic sudomotor function
◦ QSART

48.  Screening laboratory tests may be
considered for all patients with DSP (Level
C).
 Tests with the highest yield of abnormality:
1. blood glucose (fasting)
2. serum B12 with metabolites
(methylmalonic acid, homocysteine)
3. SPEP(serum protein electrophoresis)
(Level C).

49.  ANA, RF, Anti-dsDNA, Anti-Ro, Anti-La,
ANCA screen, cryoglobulins
 Urine for heavy metals, porphyrins
 IFE/urine IFE/ plasma light chain analysis

50.  BLOOD
 TC,DC,ESR
 Urea,electrolytes,LFT
 RBS,HbA1C
 Serum protein electrophoresis
 Auto Ab=ANA,Antiganglioside,Antineuronal
 Vit B 12 level
 DNA analysis=chr 17 duplication-HMSN1&1A
 =chr 17 deletion -HLPP

51.  URINE
 BJ protein
 Porphyria
 Heavy metals
 CSF ANALYSIS
 NERVE CONDUCTION STUDY
 Variation in axonal,demyelinating neuropathy
 Conduction block-CIDP,GBS,MMN
 EMG-muscle denervation changes
 Sensory threshold
 Thermal & vibration threshold

52. Antibodies against Gangliosides

GM1 : Multifocal motor neuropathy

GM1, GD1a : Guillain-Barré syndrome

GQ1b : Miller Fisher variant
Antibodies against Glycoproteins

Myelin-associated glycoprotein : MGUS
Antibodies against RNA-binding proteins

Anti-Hu, antineuronal nuclear antibody 1: Malignant
inflammatory polyganglionopathy

53.  (1) Confirming the presence of neuropathy,
 (2) Locating focal nerve lesions,
 (3) Nature of the underlying nerve pathology

55. Distal motor latency prolonged
Nerve conduction velocity slow
Reduced action potential

56.  The limitations of EMG/NCS should be
taken into account when interpreting the
findings.
◦ There is no reliable means of studying proximal
sensory nerves.
◦ NCS results can be normal in patients with small-
fiber neuropathies
◦ Lower extremity sensory responses can be absent
in normal elderly patients.
 EMG/NCS are not substitutes for a good
clinical examination.

57. IMAGES
 CXR-sarcoidosis,malignancy
 Skeletal survey-multiple myeloma
 Screening for malignancy
 AUTONOMIC FUNCTION TESTS
 Diagnostic tests imp in
 Asymmetric,motor
predominant,rapid onset,demyelinating
neuropathy

58. VASCULITIS GIANT AXONAL NPthy
AMYLOIDOSIS Infantile neuroaxonal
dystrophy
SARCOIDOSIS CMT 1&3
LEPROSY CIDPolyradiculoneuropathy
KRABBE’S Paraprotein neuropathy
METACHROMATIC
LEUKODYSTROPY

59.  In vasculitis, amyloid neuropathy, leprosy, CIDP,
Inherited disorders of myelin, and rare
axonopathies
 The Sural nerve is selected most commonly
 The superficial peroneal nerve – alternative;
:advantage of allowing simultaneous biopsy of
the peroneus brevis muscle through the same
incision.
 This combined nerve and muscle biopsy
procedure increases the yield of identifying
suspected vasculitis

60. “For symptomatic patients with suspected
polyneuropathy, skin biopsy may be
considered to diagnose the presence of a
polyneuropathy, particularly SFSN.”

61.  Slow progression
◦ Treat causative factors if possible
◦ If rapidly progressing
 IVIG
 Immunomodulating agents
 Symptom Management

62.  Tricyclic antidepressants
◦ Amitryptilin, nortryptilin
 Calcium channel alpha-2-delta ligands
◦ Gabapentin, pregabalin
 SNRI’s
◦ Duloxetine, venlafaxine
 Topical Agents
◦ Lidocaine, Capsaicin

63.  Antiepileptic Drugs
◦ Carbamazepine, phenytoin, lacosamide
 SSRI’s
 Opioid analgesics
 Tramadol
 Miscellaneous
◦ Botulinum toxin
◦ Mexiletine
◦ Alpha lipoic acid

64.  Physical Therapy
◦ Gait and balance training
 Assistive devices
 Safe environment
 Footwear at all times
 Foot hygiene

66. Thanks