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%
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: 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.
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