Post on 03-Jun-2018
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A 62 yr old patient from Akmeemana presenting with
limb weakness
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HistoryP/C
Progressive weakness of LL for 6 wks &Progressive weakness of UL for 2 wks
H/P/CWell 5 months backDeveloped upper abdominal pain
Episodic & lasted for 3 months Ass. with nausea, vomiting, & constipationTreatment taken but poor responseGradually subsided
Developed LL & UL weaknessGradual onset
Ascending type & symmetricalCalf thigh hand
Ass. with paraesthesiae ( pins & needles ), unsteady gait
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H/P/C ctd.No urinary incontinence / retention
No double visionSpeech normalNo bulbar symptomsNo headache or fits
No feverNo SOB, coughNo palpitations or fainting attacksNo diarrhoea or constipation
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P/M/H
Nothing significantNo similar illness
F/HNo significant illnesses
Drug history Antacid medication
S/HFarmer
UnmarriedOcc. AlcoholicNo exposure to pesticides or other toxinsDiet- adequate
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Examination
GeneralNot dyspnoeic
AfebrileNot pale, not cyanosed & anictericNo clubbingNo lymphadenopathyNo skin rashes or ulcers
No fasciculations
CVS/ Res / Abd NAD
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CNSHigher functions normalCranial nerves- B/L mild facial weaknessMotor
Wasting of calf & thigh muscles & small muscles of handsNo fasciculationsTone reduced in LL & distal ULPower grade 1 in LL & grade 2 distally in ULReflexes B/L BJ & TJ reduced , others absentPlantar down
SensoryTouch, JPS & vibration absentPain & temp. present
Fundus NADSingle breath count- 24
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Summary
A 62 yr. old farmer presents with gradual onsetof ascending type of progressive limb weaknessof 6wks. duration, preceded by a significantabdominal pain. On examination he hassymmetrical motor weakness of both upper &lower limbs, hyporeflexia & areflexia, -veBabinski response & mild B/L facial weaknesswithout bulbar or respiratory muscleinvolvement. Sensory system examinationrevealed impaired touch, JPS & vibrationsensation with intact pain & temp. andautonomic functions.
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DDCIDPGBSParaneoplasticPorphyria
Toxins Pb / As
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InvestigationsFBC
WBC- 7.3x10 /mm3Hb%- 13.5 g/dlPlt.- 375,000
BP - normalFBS - 5.2 mmol/lESR - 1 st hr 12mmLFT - normalRFT - normalSE - Na- 142 , K- 4.3 mmol/lS.Ca - 9.1 mg/dlS. protien- Total-72g/l Alb-43 g/lCXR NADUSS - NADUrinary PBG - Negative
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CSFProtein- 184mg/dlCells - polymorphs-0 lymphocytes-0Sugar 5 mmol/l
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NCSDL NCV Amp CMAP
AreaCMAPDura.
L/ulnar 6.2 32.9 P 2.5D 0.6
P 12.4D 3.5
P 8.7D 9.5
R/ulnar 5.7 38 P 2.5D 0.5
P 10.0D 2.7
P 7.4D 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
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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
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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
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Conduction block & temporal dispersion isfound in all 3 nerves.
CB = proximal/distal CMAP area ratio 1.15
F response ( prolonged late response) not measured
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Chronic inflammatorydemyelinating polyneuropathy
CIDP
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Outline
General Clinical Manifestations Diagnosis
Treatment and prognosis
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CIDP
Acquired, immune-mediated polyradiculoneuropathy
Heterogeneous disorder with a wide range of clinical
expression ranging from subacute to a progressive orrelapsing-remitting course
Diagnosis is based on
clinical symptoms and signs,electrodiagnostic studies, CSF examination, and other laboratory tests
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CIDP: Incidence
In one study, prevalence was estimated to range from 1-7.7 per 100,000
These are likely underestimates, since the criteria toselect cases were strict
CIDP accounted for 13% of patients seen in oneneuromuscular center
Incidence increases with increasing ageChildren are rarely affected
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CIDP: Pathophysiology
In one study, CIDP occurred within a few weeksafter an infectious event in 16% of the patients
Because of the insidious onset, documenting
precipitating illnesses or events is very difficultBoth respiratory and gastrointestinal infectionshave been cited, but no causative organism hasbeen identifiedWith Guillain-Barre syndome, the most commonpreceding infection is Campylobacter
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CIDP: Clinical Manifestations
Slow progressive course in approximately 2/3 of cases
Relapsing course with partial or complete recoverybetween recurrences is seen in approximately 1/3 of cases
Periods of worsening and improvement usually lastweeks or monthsYoung patients tend to have a higher frequency of
relapsing course
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CIDP: Regional Variants
The classical phenotype that suggests CIDP is thepresence of proximal and distal weakness, with large fibersensory loss and areflexia
Few patients present with classic symtpoms
Subclassifications based on the clinical phenotype in orderto aid in diagnosis and treatment
Currently these subclasses are not thought to be distinctdiseases
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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 maindiagnosis to separate those cases from the idiopathicvariety
Example: CIDP with HIV infection
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CIDP: Associated Conditions
MGUSEvidence suggests that CIDP with IgM MGUS hasspecific clinical and electrophysiologic characteristics
Usually predominance of distal weakness withsensory symptoms greater than motor
Multiple sclerosisReports describe CNS white matter changes in
patients with CIDPWhether a true association exists between CIDP and
multiple sclerosis remains unclear
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CIDP: Associated Conditions
Systemic lupus erythematosus
Chronic active hepatitis (B or C)CIDP associated with hepatitis should be differentiatedfrom cryoglobulinemic vasculitisThe latter causes either symmetric distal sensorimotorpolyneuropathy or mononeuropathy multiplex but on
pathologic examination shows wallerian degenerationand not the segmental demyelination seen in CIDP
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CIDP: Associated Conditions
Inflammatory bowel diseaseCrohn disease and other inflammatory bowel conditions,although no direct correlation between the two afflictionsis knownThe mechanism an autoimmune abnormality?
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CIDP: Associated Conditions
Diabetes mellitusIncreasing evidence supports the suggestion that somepatients with diabetes who have severe neuropathy orunusually progressive neuropathy may have CIDP
superimposed on their diabetic disorderDiabetes may predispose patients to CIDP
Pregnancy
Known to worsen CIDPWorsening usually occurs in the third trimester or in
the postpartum period
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CIDP: Diagnosis
Because of the clinical heterogeneity and the lack of adiagnostic test, various diagnostic criteria have beenproposed
In one series of patients all of whom had proximal anddistal weakness and in whom 95% of patients hadimprovement with treatment, only 30% had the classictriad of slow nerve conduction velocity, elevated CSFprotein and demyelination on nerve biopsy
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American Association of Neurology: Criteria
Developed criteria for the identification of patients with CIDP forresearch studies
Pathologic criteria
Electrophysiologic criteria:Require 3 demyelinating range abnormalities in motor nerves1. Slow conduction velocity,2. Prolonged distal motor latencies ,3. F wave latencies or4. Conduction block in 2 nerves
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CIDP: EMG
Critical test to determine whether the disorder is truly a peripheralneuropathy and whether the neuropathy is demyelinating
Findings of a demyelinating neuropathyMultifocal conduction block or temporal dispersion of compound
muscle action potentialProlonged distal latenciesConduction velocity slowing to less than 75% of normal
Absent or prolonged F wave latencies
As the disease progresses, patients tend to developsecondary axonal degeneration
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CIDP: Peripheral nerve biopsy
IndicationsPatients in whom the diagnosis is not completely clearCases where other causes of neuropathy (eg,hereditary, vasculitic) cannot be excludedCases where profound axonal involvement is observedon EMGSome experts recommend biopsy for most patients priorto initiating immunosuppressive therapy
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CIDP: Histologic Findings
Interstitial and perivascular infiltration of theendoneurium with inflammatory T cells andmacrophages with local edema
Evidence exists of segmental demyelination andremyelination with occasional onion bulbformation, particularly in relapsing cases
Some evidence of axonal damage also isobserved, with loss of myelinated nerve fibers
The inflammatory infiltrate with neutrophilinfiltration is observed in only a minority of patients
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CIDP: Histology
Note the decreaseddensity of nerve fibers(arrows)
Demyelinated fibers (D) Fibers undergoing active
macrophagemediateddemyelination (M)
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Other tests
Hepatitis screen, ESR, antinuclear antibody, biochemistry profile, serum and urine immunoelectrophoresis
are necessary to exclude important associatedsystemic disorders
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CIDP: Therapy
1. Prednisolone,2. IVIg and3. Plasmapheresisall 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 treatmentand most require ongoing treatment
Early treatment is advisable to prevent axonal loss and motor neuronloss which leads to functional decline
May be irreversible
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CIDP: Therapy
Response is measured by improvement or stabilization ofpreviously documented progressive weakness, sensoryloss, or ataxia
In responsive patients, treatment is continued until maximalimprovement or stabilization is achieved, at which point itcan be tapered or discontinued
If there is further deterioration or a relapse, the therapy canbe re-instituted
Patients with chronic progressive disease requiremaintenance therapy, although tapering the treatment canbe re-attempted periodically to determine continued need
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CIDP: Therapy
PrednisoloneFirst line therapy
Agents used for refractory patients
CyclosporinCyclophosphamide
AzathioprineMycophenolate
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CIDP: Plasmapheresis
Several controlled studies confirmed benefit Proposed mechanism
Removal of antibodies and complement componentsthat are responsible for immune-mediated damage ofperipheral nerves
Has been shown to have similar efficacy as IVIg intreatment of CIDP
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CIDP: Plasmapheresis
Treatment regimensNot standardized due to a lack of controlled studiesCommon regimen
3 plasma exchanges per week for first 2 weeks Additional treatment is determined by clinical
response
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CIDP: Therapy
Neuropathic pain Antiepileptics
Carbamazepine
GabapentinTricyclic antidepressants Amitriptyline
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CIDP: Prognosis
The outcome of CIDP is difficult to predict owing to thevariety of clinical patterns and evolution
If left untreated, it can become disabling, with loss of abilityto ambulate, work, or function independently
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Thank you
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References
Acquired demyelinating neuropathy. Brain. 119. 257 270. Ad Hoc Subcommittee of the American Academy of
Neurology, AIDS Task Force (1991). Research criteria fordiagnosis of chronic inflammatory demyelinatingpolyradiculoneuropathy (CIDP). Neurology . 41. 617 618.