History :

● Onset, course, (if improvement with a drug : exact chronology )

● Topographic( lower or upper limb,focal or multifocal proximal or distal , motor or
sensory or sensorimotor or autonomic, symmetrical/asymmetrical, ) positive and
negative sensory n motor .
● Inquire if the patient has had fainting spells or orthostatic lightheadedness, heat
intolerance, or any bowel, bladder, or sexual dysfunction.
● Cranial nerve
● Truncal weakness
● Neck extensor/flexor weakness
● Metabolic, drug, systemic
● The presence of costitutional symptoms such as weight loss, malaise, and anorexia
suggests an underlying systemic disorder as a cause of the polyneuropathy. Inquiry
should be made about preceding or concurrent associated medical conditions
(diabetes mellitus, hypothyroidism, chronic renal failure, liver disease, intestinal
 malabsorption, malignancy, connective tissue diseases, human immunodeficiency
virus [HIV] seropositivity); drug use, including over-the-counter vitamin preparations
(vitamin B6 ); alcohol and dietary habits; and exposure to solvents, pesticides, or
heavy metals.
● Injury on toes( anterior in LMN)
● When mentioning weaknesss, history of incordination should be taken
simultaneously.
● Trophies ulcer, cotton wool sensation
● Fasciculations:: on history Twitching of muscles and worsening severity to be
quantified..

Examination:
Gen physical examination

1) thickened nerves

Leprosy, CIDP, amyloidosis, HNPP, Refsum’s disease

Focal: neurofibromatosis
2) Maculoanesthetic patches: leprosy
3) Umbilical keratoma: Fabry
4) Orange tonsil : tangier
 5) Mees lines:arsenic, thallium
6) Musculoskeletal abnormality, high arched palate, pes cavus,mutilation: hereditary
neuropathy
7) Pseudoathetosis
8) orthostatic hypotension without a compensatory rise in heart rate when autonomic
fibers are involved.
9) Respiratory rate and vital capacity should be evaluated in Guillain-Barré syndrome to
assess for respiratory compromise.
10) The presence of lymphadenopathy, hepatomegaly or splenomegaly, and skin lesions
may provide evidence of systemic disease
11) Alopecia: thallium
12) Tightly wound curls: giant axonal neuropathy
13) Purpuric rashes in lower limbs: cryoglobulinemia
14) Icthyosis Refsum’s disease

Timeline :;acute vs subacute vs chronic

Hyper acute: vasculitic
Acute: AIDP, acute arsenic
Subacute: SIDP
Chronic: CIDP
Course:
Relapsing remitting:A relapsing course is found in chronic inflammatory demyelinating
polyradiculoneuropathy (CIDP), acute porphyria, Refsum disease, hereditary neuropathy
with liability to pressure palsies (HNPP), familial brachial plexus neuropathy, and repeated
episodes of toxin exposure.

Progressive:
Mononeuropathy/MNM/ polyneuropathy (topography)

Mononeuropathy: trauma, compression or entrapment ; may occur as part of HNPP,

amyloidosis
Also seen in RA, myxedema, acromegaly. Can be seen in leprosy, DM, vasculitis,
sarcoidosis.

Mononeuritis multiplex:involvement of multiple separate non contiguous peripheral nerves

either simultaneously or sequentially
Causes: leprosy, vascultis
Multifocal pattern can be seen in : vasculitis, DM, HIV,leprosy , HNPP, multifocal variant of
CIDP and sarcoidosis

Proximal vs distal
Early proximal: inflammatory neuropathy, porphyria
Demyelinating vs axonal
In the former widespread reflex loss( even in muscles that are not particularly weak or
wasted), thickened palpable nerves, neuropathic tremor.
Uniform slowing CMT 1 , CMT X, refsum, leukodystrophy,
Acute : diphtheria, GBS. Chronic:: CIDP, dysproteinemia, osteosclerotic myeloma.
30% of vasculitic neuropathy can be demyelinating
Tacrolimus can cause a demyelinating neuropathy, mimicing CIDP
(TNF alpha inhibitors can also cause CIDP - etanercept, inflicimab, adalizumab )

In axonal neuropathy: length dependent, wasting , usually preserved reflex , ankle can be
lost
Types of fibres involved:

HIV and alcoholism can also cause small fibre neuropathy

Sensory vs motor

Purely motor:
1) MMNCB
2) Lead intoxication , dapsone , delayed op induced
3) Acute porphyria
 4) Heriditary motor neuropathy
5) At presentation: GBS, CIDP, HMSN
6) Tangier
Purely sensory:
1) Subacute sensory neuropathy caused by paraneoplastic or autoimmune dorsal root
ganglionopathies
2) CANOMAD
3) CANDA
4) CISP
5) Doxorubicin, vitamin e def, pyridoxine overdose-causes of ganglionopathy
Sensory predominant: Common pattern , sjogren syndrome, dysproteinemia, acquired
immunodeficiency syndrome (AIDS), vitamin B 12 deficiency, celiac disease, inherited and
idiopathic sensory neuropathies, and intoxications with cisplatin, thalidomide, or
pyridoxinesyndrome, dysproteinemia, acquired immunodeficiency syndrome (AIDS), vitamin
B 12 deficiency, celiac disease, inherited and idiopathic sensory neuropathies, and
intoxications with cisplatin, thalidomide, or pyridoxine. Ass with Castleman disease..
Motor predominant: DADS , CMT ,[Motor deficits tend to dominate the clinical picture in
acute and chronic inflammatory demyelinating polyneuropathies, hereditary motor and
sensory neuropathies, and in neuropathies associated with osteosclerotic myeloma,
porphyria, lead toxicity, organophosphate intoxication, and hypoglycemia]

Mixed:

Distal symmetric polyneuropathy with motor greater than sensory involvement suggests a
distinct differential diagnosis. The most common cause of this pattern is Charcot-Marie-Tooth
disease (CMT), also known as hereditary motor sensory neuropathy.
Symmetrical vs assymetrical
Heriditary:HNPP, CMTX - asymmetrical

With autonomic
1) diabetes
2) GBS
3) Small fibre neuropathy
4) HIV
5) Porphyia
6) Tangier’s disease
7) Cisplatin , vinca alkaloids
With cranial nerve
1) Anosmia: refsum, b12 def
2) Optic disc pallor:leukodystrophy,vitamin b 12 deficiency
3) Optic atrophy CMT 2A
4) Pigmentary retinal degeneration: Refsum’s disease
5) Impaired light reflex, dysautonomia
6) External opthalmoplegia: Miller Fisher
7) Facial weakness : GBS
8) Trigeminal sensory loss: Sjögren’s syndrome
9) Lower cranial palsy with gynaecomastia: Kennedy syndrome
10) Diabetes
Upper limb
GBS, CIDP, lead, porphyria, HNPP
With CNS involvement:
Vitamin b 12 def
Adrenomyeloneuropathy
Acanthocytosis
HIV, syphillis
Hypothyroidism
Giant cell neuropathy

Ganglionopathies:
Sjögren’s syndrome
Platinum containing chemotherapeutics
Paraneoplastic
Vitamin b6 toxicity
HIV

With heriditary ataxia:

Friedrich’s ataxia::sensory predominant, early lower limb areflexia with pes cavus and
hammer toes
SCA: 33,4,18,25
With pain:
Drugs:
Points to rem:
● MC pattern is distal symmetrical: metabolic, toxic ,systemic are common causes
● Mononeurits in a non entrapment site, consider evolving mononeuritis multiplex
● Most drugs cause axonal neuropathy , except amiodarone, chloroquine, suramin and
gold which cause demyelinating and platinum containing chemotherapeutic
agents,thalidomide and pyridoxine which cause ganglionopathy
● Distal dying back seen in axonal neuropathy, but can be seen in demyelination
because in a diffuse process, longer fibres have a greater chance of being affected
● Multisegemental pattern of sensory involvement , including trunk suggests dorsal root
ganglionopathies
● Long standing mononeuritis, can become symmetrical due to extensive nerve
involvement, termed confluent mononeuritis multiplex
● Autonomic neuropathies should be suspected on the basis of the features of
orthostatic hypotension, hyperhydrosis, genitourinary symptoms (impotence,
nocturia, retention of urine), gastrointestinal (constipation, postprandial fullness,
 diarrhea) and worsening of the symptoms on bed rest, alcohol, hot bath, exercise
and hyperventilation
● standing or vertical tilt (Normal fall, <20/10 mmHg), heart rate response to standing
(increase, 11–90 beats/min; 30:15 ratio ≥ 1.04), isometric exercise (normal increase
in diastolic blood pressure, 15 mmHg), heart rate variation with respiration (normal,
≥15 beats/min, inspiratory expiratory ratio 1.2), valsalva ratio (N≥1.4), cold pressure
test (after 1 min systolic blood pressure, 15–20 mmHg/diastolic 10–15 mmHg), sweat
test, axon reflex (piloerection, sweating), pupillary tests, Schirmer's test (15 mm after
5 min). Autonomic function can also be evaluated by sympathetic skin response
● First line investigation:Blood count, ESR, Blood sugar,Liver and renal function
tests,Serum vitamin B12,Paraprotein levels,Thyroid function tests, Vasculitis profile
● CSF is useful in CIDP, AIDP and chronic immune-mediated axonal neuropathies
where the levels of CSF protein are elevated. Significant pleocytosis should raise the
suspicion regarding other acute inflammatory neuropathies such as Borrelia,
sarcoidosis or HIV virus
● CMT 1A patients are susceptible to severe reaction to vincristine and other
chemotherapeutic drugs.
● In Neuronopathies Because the injury is at the level of the cell body, recovery is often
incomplete
● Predominantly motor neuropathies are often proximal and include acquired
inflammatory neuropathies such as Guillain-Barré syndrome.An exception is lead
neuropathy, which initially affects motor fibers in radial and peroneal distributions.
● Most toxic and metabolic neuropathies are initially sensory and later may involve the
motor fibers
● Pure sensory neuropathies or neuronopathies can result from drug toxicity (e.g.,
thalidomide, cisplatin [Platinol]), paraneoplastic syndromes or nutritional deficiencies
● Diabetes, HIV infection and alcoholism can cause several patterns of neuropathy.
They most commonly cause a distal, symmetric axonal sensorimotor neuropathy.
● The second most common presentation in these conditions is a small-fiber, painful
neuropathy. Involvement of autonomic fibers is common in diabetes but less common
in acquired immunodeficiency syndrome (AIDS) or alcoholism.
● These three patterns of neuropathy occur only in the AIDS stage of HIV infection.
Medications used to treat HIV infection, such as didanosine (ddI; Videx) and
zalcitamine (ddC; Hivid) also cause a distal symmetric axonal sensorimotor
neuropathy.
● 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). Patients may complain of pain
with innocuous stimuli such as sheets rubbing over their feet (allodynia)
● Peripheral neuropathy can present as restless leg syndrome.
● Trophic changes are most prominent in diabetes, amyloid neuropathy, leprosy,
hereditary motor sensory neuropathy (HMSN) with prominent sensory involvement,
and hereditary sensory neuropathy
● HIV poly radiculopathy. or mono neuritis multiplex:: always rule out CMV
● Autonomic dysfunction in the absence of diabetes should alert the clinician to the
possibility of amyloid polyneuropathy, an autoimmune small fiber ganglionopathy, or
in a young child, hereditary sensory and autonomic neuropathy (HSAN)
● Unilateral combined motor and sensory presentations in a single extremity are
usually due to a simple entrapment or compressive neuropathy or radiculopathy.
● Approximately 20-30% of patients with vasculitis of the peripheral nervous may
present with a distal, symmetric motor and sensory dysfunctionrather than with
asymmetric, multiple mononeuropathies. The clue to diagnosing these patients is the
subacute evolution over weeks with severe pain and prominent motor involvement,
features which help make the distinction from metabolic,toxic or heriditary disorders.
● Neuropathic pain can be burning, dull and poorly localized (protopathic pain),
presumably transmitted by polymodal C nociceptor fibers, or sharp and lancinating
(epicritic pain), relayed by Aδ fibers.
● The cryptogenic sensory polyneuropathy (CSPN) , vasculitic neuropathy and
neuropathy due to diabetes mellitus are the most common neuropathies that are
associated with severe pain.
● If the neurologic examination reveals a dramatic asymmetric loss of proprioception
with significant vibration loss and normal strength, the clinician should immediately
consider a sensory neuronopathy (i.e., ganglionopathy).
● A variant of CIDP termed chronic immune sensory polyradiculopathy (CISP)
manifests as sensory ataxia and clinically resembles a sensory
neuronopathy/ganglionopathy.
● The discordance between sensory ataxia and loss of reflexes but normal SNAPs
should make one consider CISP. Although the SNAPs may be normal, often the H-
reflexes are prolonged or absent as may be more proximal potentials on
somatosensory evoked potentials due to proximal demyelination of the sensory roots.
● profound proprioception and vibration loss can also be due to posterior column
damage from disorders such as combined system degeneration.
● However, posterior column myelopathy is generally symmetric, in general is less
profound than most of the patients with true dorsal root ganglion loss and is often
associated with evidence of upper motor neuron pathology (see below). One notable
exception is Vitamin E deficiency which can affect both sensory nerves and posterior
columns and produce a profound symmetric proprioceptive deficit.
● Using a clock, one determines how long the patient can perceive the vibratory
stimulus. In children and young adults, this maximal vibratory stimulus is appreciated
for at least 15 seconds over the great toe. As patients age, this time decreases even
in the absence of overt peripheral neuropathy. As a basic rule of thumb, we allow 1
second of vibration perception loss per decade.
● Presence of UMN signs in a patient with symmetrical distal sensory motor
involvement suspect: b12 def, HIV, Cu deficiency,adrenomyeloneuropathy .
● Numb hand syndrome: sensory disturbance in hand before feet in b12 def
● Mononeuritis multiplex is usually an axonal process, but multifocal acquired
demyelinating sensory and motor neuropathy and hereditary neuropathy with liability
to pressure palsies are multifocal demyelinating neuropathies.
● Proprioception is often involved early in disorders affecting the dorsal columns and
late in disorders affecting the peripheral nerves.
● Climbing up -hip extensor, climbing down quadriceps
● Dying back phenomena:: axoplasmic flow
● Asymmetric rapid/change in progression : vasculitis.
● DADS Parapoteinemias