A 62 yr old patient from

Akmeemana presenting with

limb weakness

History
P/C
Progressive weakness of LL for 6 wks &
Progressive weakness of UL for 2 wks
H/P/C
Well 5 months back
Developed upper abdominal pain
Episodic & lasted for 3 months
Ass. with nausea, vomiting, & constipation
Treatment taken but poor response
Gradually subsided
Developed LL & UL weakness
Gradual onset
Ascending type & symmetrical
Calf thigh hand
Ass. with paraesthesiae ( pins & needles ), unsteady gait
H/P/C ctd.
No urinary incontinence / retention
No double vision
Speech normal
No bulbar symptoms
No headache or fits
No fever
No SOB, cough
No palpitations or fainting attacks
No diarrhoea or constipation

P/M/H
Nothing significant
No similar illness

F/H
No significant illnesses

Drug history
Antacid medication

S/H
Farmer
Unmarried
Occ. Alcoholic
No exposure to pesticides or other toxins
Diet- adequate

Examination
General
Not dyspnoeic
Afebrile
Not pale, not cyanosed & anicteric
No clubbing
No lymphadenopathy
No skin rashes or ulcers
No fasciculations

CVS/ Res / Abd NAD

CNS
Higher functions normal
Cranial nerves- B/L mild facial weakness
Motor
Wasting of calf & thigh muscles & small muscles of hands
No fasciculations
Tone reduced in LL & distal UL
Power grade 1 in LL & grade 2 distally in UL
Reflexes B/L BJ & TJ reduced , others absent
Plantar down
Sensory
Touch, JPS & vibration absent
Pain & temp. present
Fundus NAD
Single breath count- 24

Summary
A 62 yr. old farmer presents with gradual onset
of ascending type of progressive limb weakness
of 6wks. duration, preceded by a significant
abdominal pain. On examination he has
symmetrical motor weakness of both upper &
lower limbs, hyporeflexia & areflexia, -ve
Babinski response & mild B/L facial weakness
without bulbar or respiratory muscle
involvement. Sensory system examination
revealed impaired touch, JPS & vibration
sensation with intact pain & temp. and
autonomic functions.
DD
CIDP
GBS
Paraneoplastic
Porphyria
Toxins Pb / As
Investigations
FBC
WBC- 7.3x10 /mm3
Hb%- 13.5 g/dl
Plt.- 375,000
BP - normal
FBS - 5.2 mmol/l
ESR - 1
st
hr 12mm
LFT - normal
RFT - normal
SE - Na- 142 , K- 4.3 mmol/l
S.Ca - 9.1 mg/dl
S. protien- Total-72g/l Alb-43 g/l
CXR NAD
USS - NAD
Urinary PBG - Negative
CSF
Protein- 184mg/dl
Cells - polymorphs-0 lymphocytes-0
Sugar 5 mmol/l
NCS
DL NCV Amp CMAP
Area
CMAP
Dura.
L/ulnar 6.2 32.9 P 2.5
D 0.6
P 12.4
D 3.5
P 8.7
D 9.5
R/ulnar 5.7 38 P 2.5
D 0.5
P 10.0
D 2.7
P 7.4
D 9.4
R/med. 10.6 33.9 P 1.1
D 2.8
P 4.8
D 4.3
P 8.1
D 8.7
Analysis of NCS

Distal latency prolongation >130%

L/ULN DL 6.2/3.3=1.88=188%
R/ULN- DL 5.7/3.3=1.73=173%
DL is prolonged
Analysis of NCS
Conduction velocity slowing < 75%

L/ULN-CV 32.9/49=0.67 = 67%
R/ULN-CV 38/49 = 0.78 = 78%
R/MN CV 33.9/49 = 0.69 = 69%

CV is slow
Conduction block & temporal dispersion is
found in all 3 nerves.
CB = proximal/distal CMAP area ratio <50%
TD = proximal/distal CMAP duration ratio >1.15

F response ( prolonged late response)
not measured
Chronic inflammatory
demyelinating polyneuropathy
CIDP

Outline
General
Clinical Manifestations
Diagnosis
Treatment and prognosis
CIDP
Acquired, immune-mediated polyradiculoneuropathy

Heterogeneous disorder with a wide range of clinical
expression ranging from subacute to a progressive or
relapsing-remitting course

Diagnosis is based on
clinical symptoms and signs,
electrodiagnostic studies,
CSF examination,
and other laboratory tests
CIDP: Incidence
In one study, prevalence was estimated to range from 1-
7.7 per 100,000
These are likely underestimates, since the criteria to
select cases were strict

CIDP accounted for 13% of patients seen in one
neuromuscular center

Incidence increases with increasing age
Children are rarely affected

CIDP: Pathophysiology
In one study, CIDP occurred within a few weeks
after an infectious event in 16% of the patients
Because of the insidious onset, documenting
precipitating illnesses or events is very difficult
Both respiratory and gastrointestinal infections
have been cited, but no causative organism has
been identified
With Guillain-Barre syndome, the most common
preceding infection is Campylobacter

CIDP: Clinical Manifestations
Demyelination
Detected on nerve conduction studies or nerve biopsy
Multifocal demyelination is a diagnostic hallmark of CIDP, but
distribution of demyelinative lesions varies among patients

Weakness
Characteristically, involves both proximal and distal muscles
Typically symmetric, but can begin asymmetrically
Lasting >8 wks
Areflexia / hyporeflexia

Sensory symptoms are common (mainly large fibre) but motor
symptoms usually predominate
Touch , JPS, vibration
Autonomic system dysfunction can occur
CIDP: Clinical Manifestations
Slow progressive course in approximately 2/3 of cases


Relapsing course with partial or complete recovery
between recurrences is seen in approximately 1/3 of cases
Periods of worsening and improvement usually last
weeks or months
Young patients tend to have a higher frequency of
relapsing course

CIDP: Regional Variants
The classical phenotype that suggests CIDP is the
presence of proximal and distal weakness, with large fiber
sensory loss and areflexia
Few patients present with classic symtpoms

Subclassifications based on the clinical phenotype in order
to aid in diagnosis and treatment
Currently these subclasses are not thought to be distinct
diseases


CIDP: Regional Variants
Distal acquired demyelinating
sensory neuropathy and
sensory CIDP
Multifocal demyelinating
neuropathy with persistent
conduction block
Distal CIDP
Sensory CIDP

ANTI-MAG (Myelin
Associated Glycoprotein)
Neuropathy
CIDP with Hypertrophic
nerves
Subacute demyelinating
polyneuropathy

CIDP: Associated Conditions
Most frequently CIDP is an idiopathic illness

Has been known to occur with several conditions
The associated condition is included in the main
diagnosis to separate those cases from the idiopathic
variety
Example: CIDP with HIV infection
CIDP: Associated Conditions
HIV infection
Mild lymphocytic pleocytosis and increased gamma
globulin level in the CSF are seen frequently

Hodgkin lymphoma
Associated neuropathy is not caused by direct infiltration
of the peripheral nerves but is a consequence of the
autoimmune cascade that occurs with this disease, but
the mechanism is not completely clear

Paraproteinemias and/or plasma cell dyscrasias
CIDP: Associated Conditions
MGUS
Evidence suggests that CIDP with IgM MGUS has
specific clinical and electrophysiologic characteristics
Usually predominance of distal weakness with
sensory symptoms greater than motor

Multiple sclerosis
Reports describe CNS white matter changes in
patients with CIDP
Whether a true association exists between CIDP and
multiple sclerosis remains unclear
CIDP: Associated Conditions
Systemic lupus erythematosus


Chronic active hepatitis (B or C)
CIDP associated with hepatitis should be differentiated
from cryoglobulinemic vasculitis
The latter causes either symmetric distal sensorimotor
polyneuropathy or mononeuropathy multiplex but on
pathologic examination shows wallerian degeneration
and not the segmental demyelination seen in CIDP
CIDP: Associated Conditions
Inflammatory bowel disease
Crohn disease and other inflammatory bowel conditions,
although no direct correlation between the two afflictions
is known
The mechanism an autoimmune abnormality?
CIDP: Associated Conditions
Diabetes mellitus
Increasing evidence supports the suggestion that some
patients with diabetes who have severe neuropathy or
unusually progressive neuropathy may have CIDP
superimposed on their diabetic disorder
Diabetes may predispose patients to CIDP

Pregnancy
Known to worsen CIDP
Worsening usually occurs in the third trimester or in
the postpartum period
CIDP: Diagnosis
The diagnosis of CIDP is typically based on
Clinical presentation,
Absence of other causes of the neuropathic syndrome, and
Results of electrodiagnostic studies


Presence of increased cerebrospinal fluid (CSF) protein
and demyelinating changes on nerve biopsy are supportive
of the diagnosis, but these are not always present
CIDP: Diagnosis
Because of the clinical heterogeneity and the lack of a
diagnostic test, various diagnostic criteria have been
proposed

In one series of patients all of whom had proximal and
distal weakness and in whom 95% of patients had
improvement with treatment, only 30% had the classic
triad of slow nerve conduction velocity, elevated CSF
protein and demyelination on nerve biopsy
American Association of Neurology: Criteria
Developed criteria for the identification of patients with CIDP for
research studies

Pathologic criteria

Electrophysiologic criteria:
Require 3 demyelinating range abnormalities in motor nerves
1. Slow conduction velocity,
2. Prolonged distal motor latencies ,
3. F wave latencies or
4. Conduction block in 2 nerves



Laboratory Studies: CSF
Protein level is increased significantly in 80% of patients
Usually between 50 and 200 mg/dL

10% of patients also have mild lymphocytic pleocytosis
(<50 cells) and increased gamma globulin (usually
associated with HIV infection)

CIDP: EMG
Critical test to determine whether the disorder is truly a peripheral
neuropathy and whether the neuropathy is demyelinating
Findings of a demyelinating neuropathy
Multifocal conduction block or temporal dispersion of compound
muscle action potential
Prolonged distal latencies
Conduction velocity slowing to less than 75% of normal
Absent or prolonged F wave latencies

As the disease progresses, patients tend to develop
secondary axonal degeneration
CIDP: Peripheral nerve biopsy
Indications
Patients in whom the diagnosis is not completely clear
Cases where other causes of neuropathy (eg,
hereditary, vasculitic) cannot be excluded
Cases where profound axonal involvement is observed
on EMG
Some experts recommend biopsy for most patients prior
to initiating immunosuppressive therapy
CIDP: Histologic Findings
Interstitial and perivascular infiltration of the
endoneurium with inflammatory T cells and
macrophages with local edema
Evidence exists of segmental demyelination and
remyelination with occasional onion bulb
formation, particularly in relapsing cases
Some evidence of axonal damage also is
observed, with loss of myelinated nerve fibers
The inflammatory infiltrate with neutrophil
infiltration is observed in only a minority of patients
CIDP: Histology
Note the decreased
density of nerve fibers
(arrows)
Demyelinated fibers (D)
Fibers undergoing active
macrophagemediated
demyelination (M)

Other tests
Hepatitis screen,
ESR,
antinuclear antibody,
biochemistry profile,
serum and urine immunoelectrophoresis

are necessary to exclude important associated
systemic disorders
CIDP: Therapy
1. Prednisolone,
2. IVIg and
3. Plasmapheresis
all been demonstrated to be effective in controlled clinical trials
In one study, response was seen to at least 1 of these 3 main
therapies in 66% of patients

Only 1/3 of patients have a sustained remission after initial treatment
and most require ongoing treatment

Early treatment is advisable to prevent axonal loss and motor neuron
loss which leads to functional decline
May be irreversible
CIDP: Therapy
Response is measured by improvement or stabilization of
previously documented progressive weakness, sensory
loss, or ataxia

In responsive patients, treatment is continued until maximal
improvement or stabilization is achieved, at which point it
can be tapered or discontinued

If there is further deterioration or a relapse, the therapy can
be re-instituted

Patients with chronic progressive disease require
maintenance therapy, although tapering the treatment can
be re-attempted periodically to determine continued need
CIDP: Therapy
Prednisolone
First line therapy
Agents used for refractory patients
Cyclosporin
Cyclophosphamide
Azathioprine
Mycophenolate
CIDP: Plasmapheresis
Several controlled studies confirmed benefit
Proposed mechanism
Removal of antibodies and complement components
that are responsible for immune-mediated damage of
peripheral nerves

Has been shown to have similar efficacy as IVIg in
treatment of CIDP
CIDP: Plasmapheresis
Treatment regimens
Not standardized due to a lack of controlled studies
Common regimen
3 plasma exchanges per week for first 2 weeks
Additional treatment is determined by clinical
response
CIDP: IV Ig
Several studies showed significant benefit in CIDP
Useful alternative to plasmapheresis

On average, improvement seen by day 10 and
continues through day 42

Serum half-life is approximately 21-29 days

Patients usually require repeated treatments every
few weeks or months to maintain remission or
treat recurrences
CIDP: Therapy
Neuropathic pain
Antiepileptics
Carbamazepine
Gabapentin
Tricyclic antidepressants
Amitriptyline
CIDP: Prognosis
The outcome of CIDP is difficult to predict owing to the
variety of clinical patterns and evolution

If left untreated, it can become disabling, with loss of ability
to ambulate, work, or function independently

Thank you
References
Acquired demyelinating neuropathy. Brain. 119. 257270.
Ad Hoc Subcommittee of the American Academy of
Neurology, AIDS Task Force (1991). Research criteria for
diagnosis of chronic inflammatory demyelinating
polyradiculoneuropathy (CIDP). Neurology. 41. 617618.