![Investigations
• CSF: Albuminocytological dissociation
-An elevated CSF protein level (1–10 g/L [100–1000 mg/dL]) without accompanying pleocytosis
-if >10 cells: HIV, CMV and other infections should be ruled out
• NCS:
In AIDP:
- The earliest features are prolonged F-wave latencies, prolonged distal latencies, and reduced
amplitudes of compound muscle action potentials (CMAPs)
- Later, slowing of conduction velocity, conduction block, and temporal dispersion may be
appreciated.
In AMAN and AMSAN:
- The principal EDx finding is reduced amplitude of CMAPs (and also SNAPS with AMSAN) without
conduction slowing or prolongation of distal latencies.](https://image.slidesharecdn.com/approachtoaidporcidp-241204160236-317647ec/85/Approach-to-Acute-inflammatory-demyelinating-polyneuropathyIDP-or-CIDP-pptx-16-320.jpg)
Approach to Acute inflammatory demyelinating polyneuropathyIDP or CIDP.pptx
- 1. Approach to a patient with AIDP or CIDP Presenter: Dr. Sani Phikow Moderator: Dr. Heli Kapoor HOD: Dr. Praveen Kr Malik Department of General Medicine, ESIC Medical College and Hospital, Faridabad
- 2. OUTLINES • GBS: - Introduction - Clinical manifestations - Risk factors - Pathogenesis - Subtypes or variants - Diagnosis and treatment • CIPD • Cases
- 3. Guillain-Barré syndrome • Introduction: - It is an acute, inflammatory, and demyelinating polyradiculoneuropathy that is autoimmune in nature - A demyelinating disease - Involves predominantly peripheral nerves and symmetrical - Males are affected more than females - 10 to 20 cases per million annually
- 4. Clinical manifestations • Motor: - A rapidly evolving areflexic motor paralysis with or without sensory disturbance - Usual pattern is an ascending paralysis (rubbery legs) - Evolves over hours to a few days and is frequently accompanied by tingling dysesthesias in the extremities - Legs are usually more affected than the arms • Sensory: - Cutaneous sensory deficits (e.g., loss of pain and temperature sensation) are usually relatively mild - Large sensory fibers, such as deep tendon reflexes and proprioception, are more severely affected - Pain in the neck, shoulder, back, or diffusely over the spine is also common in the early stages of GBS, occurring in ~50% of patients - Deep aching pain may be present in weakened muscles - Deep tendon reflexes attenuate or disappear within the first few days of onset
- 5. • Cranial Nerves: - Facial diparesis is present in 50% of affected individuals - Rarely bulbar weakness with difficulty handling secretions and maintaining an airway. requiring ventilatory support • Autonomic involvement: - Bladder dysfunction may occur in severe cases but is usually transient - Loss of vasomotor control with wide fluctuations in blood pressure, postural hypotension, and cardiac dysrhythmias - Requires close monitoring and can be fatal
- 6. Risk factors • 1-3 weeks prior to onset of disease • Mostly GI/Respiratory infections • Most common organism: Campylobacter Jejuni - A/w 76% AMAN • Mycoplasma, HIV, EBV, CMV, Zika can also be present • Vaccine associated (influenza, meningococcal, SARS covid, Rabies)
- 7. Pathogenesis • Molecular mimicry: - Triggered when an immune response to an antecedent infection or other event cross-reacts with shared epitopes on peripheral nerve - Immune systems recognized to myelin epitopes as ‘foreign’ and targets it for destruction • All myelinated nerves (motor, sensory, cranial, sympathetic) can be affected
- 9. Subtypes of GBS • AIDP: - Acute inflammatory demyelinating Polyneuropathy - Most common, affects adults > children - Anti GM1 antibodies • AMAN: - Acute motor Axonal neuropathy - Children and young adults, prevelant in China and Mexico - Associated with Anti GD1a antibodies, rapid recovery • AMSAN: - Acute motor and sensory axonal neuropathy - Less common but more severe and mostly adults - Can progress in < 7 days, slow recovery
- 10. Miller Fischer Syndrome • A regional GBS variant, affects adults and children • Triad of: - Ophthalmoplegia (Often with pupillary paralysis) - Ataxia (Rapidly evolving) - Areflexia (Without weakness) • Associated with Anti-GQ1b antibodies • Can be axonal or demyelinating
- 11. Brighton Criteria for Diagnosis of Guillain-Barré Syndrome (GBS) • Level 1 of diagnostic certainty: - Bilateral AND flaccid weakness of the limbs - AND Decreased or absent deep tendon reflexes in weak limbs - AND Monophasic illness pattern and interval between onset and nadir of weakness between 12 h and 28 days and subsequent clinical plateau - AND Electrophysiologic findings consistent with GBS - AND Cytoalbuminologic dissociation (i.e., elevation of CSF protein level above laboratory normal value AND CSF total white cell count <50 cells/μL) - AND Absence of an identified alternative diagnosis for weakness
- 12. • Level 2 of diagnostic certainty: (Investigation Based) - Bilateral AND flaccid weakness of the limbs - AND Decreased or absent deep tendon reflexes in weak limbs - AND Monophasic illness pattern and interval between onset and nadir of weakness between 12 h and 28 days and subsequent clinical plateau - AND CSF total white cell count <50 cells/μL (with or without CSF protein elevation above laboratory normal value) - OR If CSF not collected or results not available, electrophysiologic studies consistent with GBS - AND Absence of identified alternative diagnosis for weakness
- 13. • Level 3 of diagnostic certainty: (EXCLUSION based) - Bilateral and flaccid weakness of the limbs and Decreased or absent deep tendon reflexes in weak limbs - AND monophasic illness pattern and interval between onset and nadir of weakness between 12 h and 28 days and subsequent clinical plateau - AND Absence of identified alternative diagnosis for weakness
- 14. Diagnostic certainty of Miller Fisher Syndrome: • Bilateral ophthalmo-paresis and bilateral reduced or absent tendon reflexes, and ataxia AND Absence of limb weakness • AND Monophasic illness pattern and interval between onset and nadir of weakness between 12 h and 28 days and subsequent clinical plateau • AND Cyto albuminologic dissociation (i.e., elevation of cerebrospinal protein above the laboratory normal and total CSF white cell count <50 cells/μL) • AND Nerve conduction studies are normal, OR indicate involvement of sensory nerves only • AND No alterations in consciousness or corticospinal tract signs • AND Absence of identified alternative diagnosis
- 15. Differential Diagnosis • Acute myelopathies (especially with prolonged back pain and sphincter disturbances) • Diphtheria (early oropharyngeal disturbances) • Lyme poly-radiculitis and other tick-borne paralyses • Porphyria (abdominal pain, seizures, psychosis) • Vasculitis neuropathy (raised erythrocyte sedimentation rate) • Poliomyelitis and acute flaccid myelitis (wild-type poliovirus, West Nile virus, entero-virus D68, enterovirus A71, Japanese encephalitis virus, and the wild-type poliovirus) • CMV poly-radiculitis (in immunocompromised patients) • Neuromuscular junction disorders such as myasthenia gravis and botulism (pupillary reactivity lost early) • Poisonings with organophosphates, thallium, or arsenic; paralytic shellfish poisoning, or severe hypophosphatemia
- 16. Investigations • CSF: Albuminocytological dissociation -An elevated CSF protein level (1–10 g/L [100–1000 mg/dL]) without accompanying pleocytosis -if >10 cells: HIV, CMV and other infections should be ruled out • NCS: In AIDP: - The earliest features are prolonged F-wave latencies, prolonged distal latencies, and reduced amplitudes of compound muscle action potentials (CMAPs) - Later, slowing of conduction velocity, conduction block, and temporal dispersion may be appreciated. In AMAN and AMSAN: - The principal EDx finding is reduced amplitude of CMAPs (and also SNAPS with AMSAN) without conduction slowing or prolongation of distal latencies.
- 17. Treatment • Initiated ASAP after diagnosis and each day counts • If the patient has already reached the plateau stage, then treatment probably is no longer indicated, unless the patient has severe motor weakness and one cannot exclude the possibility that an immunologic attack is still ongoing • Either high-dose intravenous immune globulin (IVIg) or plasmapheresis (PLEX) can be initiated, as they are equally effective for typical GBS • IVIg: - It is the initial therapy chosen because of its ease of administration and good safety record - Dose: five daily infusions for a total dose of 2 g/kg body weight or 0.4g/kg/day • PLEX: Usually consists of ~40–50 mL/kg plasma exchange (PE), 4–5 times over 7– 10 days.
- 18. • Supportive Treatment: - In the worsening phase of GBS, most patients require monitoring in a critical care setting, with particular attention to vital capacity, heart rhythm, blood pressure, nutrition, deep-vein thrombosis prophylaxis, cardiovascular status, early consideration (after 2 weeks of intubation) of tracheotomy, and chest physiotherapy. • Prognosis & Recovery: - Approximately 85% of patients with GBS achieve a full functional recovery within several months to a year - Mortality rate is <5% in optimal settings; death usually results from secondary pulmonary complications - ~30% of patients with GBS require ventilatory assistance, sometimes for prolonged periods of time
- 19. CIDP(Chronic inflammatory demylelinating Polyneuropathy) • Definition: - An inflammatory and albumin cytological dissociation - Insidious onset and gradually progressive - Relapses at least 3 times - Duration is >9 weeks in CIDP and < 4weeks in GBS - Steroid responsive in CIDP but no roles in GBS
- 20. Clinical features • Presentations of CIDP: - Acute CIDP: 2% of GBS can present like Acute CIDP - Progressive type:60% of cases , stepwise or continouos progression, more common in older age group - Relapsing or remitting • Symptoms: - Proximal + Distal weakness (Proximal > distal) - Facial involvement: <5% CIDP cases
- 21. Variants Of CIDP • Motor CIDP • CISP(Chronic immune sensory Polyradiculopathy): normal CMAP, SNAP, enlarged roots in MRI, IVIg responsive • CILSP(Chronic inflammatory lumbosacral plexopathy):CSF proteins may be raised, presents like lumbosacral plexopathy • MADSAM(Multifocal acquired demyelinating sensory and motor neuropathy): multifocal, multiple single nerve involvement • DADS (Distal acquired symmetrical demyelinating neuropathy): sensory ataxia and distal involvement is classical presentation,2/3 is due to monoclonal gammopathy, poor response to steroids, IVIg and rituximab have good response • CANOMAD(Chronic ataxic neuropathy ophthalmoplegia disialosyl IgM antibody and cold agglutinin): IgM antibody GD1b, GQ1B, may be responsive to ivig and rituximab
- 22. Diagnostic Criteria • Mandatory Clinical criteria: - Progressive or relapsing muscle weakness for 2 months or more - Symmetrical proximal and distal weakness in upper and lower extremities - Hyporeflexia or Areflexia • Mandatory Lab criteria: - CSF protein level >45% mg/dl, Cell count <10/microL - NCS with features of demyelination( motor nerve conduction<70% of lower limit of normal) - Sural nerve biopsy with features of demyelination and remyelination including myelinated fiber loss and perivascular inflammation
- 23. • Mandatory exclusion criteria: - Evidence of relevant systemic disease or toxic exposure - Family history of neuropathy - Nerve biopsy findings incompatible with diagnosis • Diagnostic categories: - Definite: Mandatory inclusion and exclusion criteria and all laboratory - Probable: Mandatory inclusion and eclusion criteria and two of three lab criteria - Possible: Mandatory inclusion and exclusion criteria and of three laboratory criteria
- 24. Secondary CIDP • Infections: HIV, Hepatitis • Inflammatory: SLE,IBD • Drugs: Tacrolimus, Etanercept, infliximab • Metabolic disease: Diabetes • Malignancy: melanoma, Hodgkin’s, Plasmacytoma Investigations • Routine blood investigations, • Serum Protein electrophoresis • Vasculitis • CSF • NCS • Nerve Biopsy • MRI Brain • Usg
- 25. • Indication: - When progression is rapid or walking is compromised • IVIg: - Initial therapy is usually with IVIg, administered as 2.0 g/kg body weight given in divided doses over 2–5 day - Three monthly courses are generally recommended before concluding a patient has failed treatment - If the patient responds, the infusion intervals can be gradually increased or the dosage decreased (e.g., starting at 1 g/kg every 3–4 weeks) • ScIg: - Patients who require more frequent IVIg - Experience side effects with IVIg (headaches) - Have poor venous access Or find it more convenient - Dose is 2–3 times a week such that the total dosage per month is the same or slightly higher than the monthly dosage of IVIg Treatment
- 26. • PLEX: Effective as IVIg, is initiated at 2–3 treatments per week for 6 weeks • Glucocorticoids: 60–80 mg prednisone PO daily for 1–2 months, followed by a gradual dose reduction of 10 mg per month as tolerated • Immunosuppressive agents such as azathioprine, methotrexate, cyclosporine, and cyclophosphamide, either alone or as adjunctive therapy • CIDP associated with anti-CNTN1, NF155,NF140/186, and Caspr1 antibodies (IgG4 subclass antibodies) is typically refractory to IVIg, but several studies suggest a response to rituximab.
- 27. Case 1 • A 44yr old male came with history tingling and numbness of both lower limb since 10 days, noticed buckling of both knees 9 days, started having difficulty to get up from squatting since 7 days, unable to lift the upper limb since 5 days. Past h/o GI infections 2 months back • On presentation, the patient was normotensive (117/80 mmHg), afebrile (97.8 °F), and breathing comfortably (18 breaths per minute; oxygen saturation 98% on room air), with normal heart rate (78 beats per minute) • Weight upon admission was 65 kg • Physical examination revealed no toxicity, in no acute distress, without tachypnea or use of accessory muscles. Pulmonary auscultation revealed clear lungs bilaterally • Neurological examination revealed bilateral lower extremity weakness (strength 3/5), mute reflexes, stocking-glove sensory loss to pinprick and cold up to above the knees and elbows, and decreased vibratory sensation in the fingers and medial malleolus.
- 28. • Initial laboratory results demonstrated a neutrophil-predominant leukocytosis with elevated inflammatory markers. • Chest X-ray and head computed tomography were unremarkable. Brain magnetic resonance imaging revealed normal study • CSF analysis shows Albumino cytological dissociation (WBC < 5 mm3 Total protein 182 mg/dL) • NCS shows prolonged F waves and distal latencies with reduced CMAPS • Based on the clinical and laboratory findings, a preliminary diagnosis of GBS was made and the patient was started on daily intravenous immunoglobulin (IVIG) administration at a dose of 0.4 g/kg on the day of admission • Following 4 weeks of intense physical therapy, the patient was able to walk with assistance • Neurological exam revealed improvement in strength to 4/5 in all extremities.
- 29. Case 2 • A 50-year-old man received the first dose of the Ad26.COV2.S vaccine against COVID-19 seven weeks prior and experienced a tingling sensation in both legs after a week and gait disturbance three weeks after that, which further progresses to have weakness in holding the spoons. He had hypertension and no recent history of infection • Neurological examinations: - Motor: Power 3/5 in both upper limbs and 2/5 in both lower limbs - Sensory: Deficits of light touch and vibration sensation in the bilateral fingertips and below both knees - Reflexes: Areflexia in all four limbs • Blood tests revealed no abnormalities • MRI Brain and whole spine shows no abnormalities • CSF analysis: WBC < 5 mm3 ; TP 158 mg/dL • NCS: Motor demyelinating polyneuropathy was confirmed
- 30. • Diagnosis: - A case of CIDP because of the progressive symptoms lasting more than four weeks - The patient had chronic progressive symmetric distal limb weakness, sensory deficits and areflexia in all limbs lasting more than nine weeks, and the results of motor NCS were compatible with demyelinating neuropathy • IVIg was administered along with oral prednisolone. His symptoms improved, the motor power and the follow up NCS showed improvement.
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