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TREATMENT OF IMMUNE MEDIATED NEUROPATHIES

Treatment of Immune- mediated Neuropathies

Abdullah Al-Ajmi, BMBCh, FRCPC

Consultant Neurologist

Jahra Hospital

Kuwait

Stick to allotted time!

Will not cover all aspects of immune-mediated NP

IM NP

Immune- mediated Neuropathies

  • Guillain–Barré syndrome and variants
  • Chronic inflammatory demyelinating polyradiculoneuropathy and variants

  • Chronic demyelinating neuropathies distinct from CIDP
  • Neuropathies associated with systemic disorders

Immune- mediated Neuropathies

  • Guillain–Barré syndrome and variants
  • Chronic inflammatory demyelinating polyradiculoneuropathy and variants

  • Chronic demyelinating neuropathies distinct from CIDP
  • Neuropathies associated with systemic disorders

9%

Case

  • 32-y-o man
  • 10-day h/o LBP & numbness in hands & feet
  • Few days later, generalized body aches & numbness from waist down to feet
  • Then, unable to climb stairs
  • Progressive weakness
  • Bifacial weakness - LMN
  • Weakness ULs 4-/5, LLs 3/5
  • Absent DTRs
  • Equivocal plantar responses
  • Normal sensation

Progressive or relapsing pareses +/- sensory deficit AND hypo/absent DTRs

Duration ≥2 months

Duration < 2 months

+ve family history

EDX

&

CSF criteria fulfilled;

other causes excluded

EDX

criteria fulfilled (may be –ve in 1st 2 wks)

Consider hereditary NP

Consider CIDP

Consider GBS

CSF

  • Protein: 1304 mg/L

  • Cells: 25/cm; lymph 85%, neutroph 15%

MRI

  • Enhancement of ventral roots of cauda equina

15.7 ms

3.35 mV

26.5 m/s

  • Other motor responses absent
  • SNAPs absent
  • F-Waves absent
  • H-Reflexes absent

Needle EMG

  • Spontaneous activity: fibs ++
  • MUAPs morphology: normal
  • MUAPs recruitment: reduced

GBS

GBS

Diagnosis of GBS :

  • Clinical criteria
  • EDX criteria
  • Labs, including CSF

GBS

& variants

GBS

GBS - Historical Landmarks

http://www.galenusrevista.com/

https://neuromuscular.wustl.edu

1956

Effectiveness of PE was reported from France

1987

Effectiveness of PE was reported from North America

1985

MFS was reported

1986

1992

1978

The term Guillain–Barre syndrome was first used

1927

  • The diagnostic criteria proposed by NINDS

Axonal form of GBS was reported

  • Anti-GQ1b antibody in MFS was reported

  • Effectiveness of IVIg was established in Dutch study

  • Evidence that steroid is not effective for GBS was reported

References

Management of

Guillain-Barre ́ Syndrome

  • Frequent monitoring of respiratory function
  • Monitoring for autonomic dysfunction
  • Deep venous thrombosis prophylaxis
  • Treatment of constipation/ileus

GBS TREATMENT

  • Nonopioid management of neuropathic pain
  • Psychosocial support
  • Physical, occupational and speech therapy
  • Immunoglobulin (IVIg) or plasma exchange
  • Corticosteroid treatment not indicated

Disease-modifying treatment

Disease-modifying Treatment

  • Intravenous immunoglobulin (0.4 g/kg daily for 5 days)
  • Plasma exchange (200–250 ml/kg for 5 sessions)
  • Patients who are not ambulant within 2 weeks of onset
  • Both treatments hasten recovery
  • IVIg is often preferred due to ease of administration
  • Many clinicians would give IVIg to ambulant, but disabled, patients, particularly in the early stages when there is continuing disease progression

Evidence base

Evidence base

  • Combining the two treatments does not confer additional benefit.
  • Several large RCTs have demonstrated superiority of PLEX over supportive care alone in terms of improving median time to walking with aid.
  • In patients who do not benefit from one course of treatment, a further course of the same modality is recommended.

- It is of greatest benefit if instituted within 7 days, and four exchanges have been shown to be superior to two.

  • Head-to-head trials have shown equivalence of IVIg to PLEX in hastening recovery.
  • The choice between PLEX and IVIg is guided by local availability and patient co-morbid factors.

Treatment of GBS variants?

At present, the treatment strategies for AMAN and AIDP do not differ in clinical practice.

GBS variants no RCTs

Eculizumab

Eculizumab

  • Humanized monoclonal antibody against the complement protein C5
  • Trialled in patients with severe GBS
  • Two trials evaluating this drug included a small cohort, which precludes statistically valid assessment of efficacy
  • These trials do indicate that eculizumab is well tolerated in patients with GBS
  • Larger, multicentre, international trials are warranted
  • Timing: Within 2–13 days of disease onset
  • Dose: 900 mg q week for 4 weeks with antibiotic prophylaxis
  • Concurent IVIg treatment
  • No benefit at 4 weeks
  • Possibly more improvement at later times (20 to 24 weeks) after treatment

Prognosis

Predicting the clinical course and treatment response of GBS

mEGOS — modified Erasmus GBS Outcome Score

Captures:

• Age

• Preceding diarrhoea

• GBS disability score 2 weeks after hospitalization

EGRIS — Erasmus GBS Respiratory Insufficiency Score

Captures at time of hospital admission:

• Days between clinical onset of weakness

• Facial and/or bulbar weakness

• MRC sum score

Scores range from 1 to 7 and predict the clinical outcome after 6 months; a higher score corresponds to worse prognosis.

The scoring system ranges from 0 to 7, with corresponding chances of respiratory insufficiency within the first week after hospital admission from 1% to 91%.

ΔIgG

  • Increase in serum IgG levels 2 weeks after treatment with intravenous immunoglobulin.

Larger increase is associated with a better clinical outcome.

Treatment-related fluctuations

  • Treatment-related fluctuations are defined as worsening of weakness after an initial improvement or after stabilization following treatment with IVIG or PLEX
  • 10% of patients with GBS
  • Usually within the first two months after treatment is initiated
  • Treated with another course of IVIG or PLEX

CIDP

1958

Austin described cases of probable CIDP.

1975

Dyck et al introduced the name chronic inflammatory polyradiculoneuropathy and thus defined CIDP as a separate disease entity.

  • Chronic inflammatory demyelinating polyradiculoneuropathy and variants
  • Phenotype with IgG4 antibodies against nodal and paranodal proteins

Typical CIDP

Sensory-motor

Acute onset

Epidemiology

>50%

Around 18%

Clinical 

Subacute onset; motor and sensory

Symmetric; proximal and distal

Chronic onset; motor and sensory

Symmetric; usually proximal rather

than distal

IVIG, corticosteroids, and PLEX effective

Treatment response

Subcutaneous IGs

In March 2018 SCIG was approved by the FDA for maintenance treatment in adults diagnosed with CIDP

No data predict the best candidates for subcutaneous or intravenous immunoglobulin

Atypical CIDP variants

Motor

predominant

Distal predominant

(if MAG

antibodies not present)

Sensory

predominant

(including CISP)

Focal

Asymmetric

4–10%

Epidemiology

4–35%

Around 1%

2–10%

8–15%

Chronic onset; motor more than sensory

Symmetric; proximal and distal

Chronic onset; sensory more than motor

Symmetric; distal rather than

proximal

Clinical 

Chronic onset; sensory more than motor; sensory ataxia (in CISP)

Symmetric; distal rather than proximal; upper rather than lower limbs

Chronic onset; slow disease

progression; motor and sensory

Brachial or lumbosacral plexus or one or more peripheral nerves in one limb; proximal and distal;

upper and lower limbs

Chronic onset; motor and sensory

Asymmetric; distal rather than proximal; upper rather than lower

limbs

Treatment response

IVIG,corticosteroids, and PLEX effective

IVIG effective;

patients’ condition

might deteriorate after

corticosteroids

Phenotype with IgG4 antibodies against nodal and paranodal proteins

Next slide...

NF140

NF186

Neuropathic pains

Physiotherapy

Prognosis of CIDP

  • Most patients with CIDP require long-term treatment and follow-up.
  • Wean patients off immunotherapy by periodically following their clinical examinations and nerve conduction studies for worsening.
  • Dosage is individually titrated to patient response.

Conclusion

Conclusion

  • Immune-mediated neuropathies are heterogeneous groups
  • The mainstay treatments are IVIG, PLEX or steroids
  • AIDP & AMAN variants of GBS have similar treatment strategy depending on the severity
  • There are different CIDP phenotypes, some differ in treatment response
  • Depending on the severity & presence of complications, treatment involves other modalities

References

  • Bunschoten et al. Progress in diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy. Lancet Neurol. 2019 Aug;18(8):784-794.
  • Dyck et al. History, Diagnosis, and Management of Chronic Inflammatory Demyelinating Polyradiculoneuropathy. Mayo Clin Proc. 2018 Jun;93(6):777-793.
  • Kieseier et al. Immune-mediated neuropathies. Nat Rev Dis Primers. 2018 Oct 11;4(1):31
  • Russell. Approach to Peripheral Nerve Disorders. Continuum (Minneap Minn) 2017;23(5):1241–1262
  • Donofrio. Guillain-Barre Syndrome. Continuum (Minneap Minn) 2017;23(5):1295–1309
  • https://www.uptodate.com/contents/immune-mediated-neuropathies
  • https://neuromuscular.wustl.edu/
  • Bashar Katirji. Disorders of Peripheral Nerves. Bradley's Neurology in Clinical. 2016, Elsevier.
  • Allen et al. Immunoglobulin administration for the treatment of CIDP: IVIG or SCIG? J Neurol Sci. 2020 Jan 15;408:116497
  • Kusunoki. History of Guillain–Barre syndrome. Clinical and Experimental Neuroimmunology 7 (2016) 305–311
  • Drugs in Neurology 2017
  • Sonja E. Leonhard et al. Diagnosis and management of Guillain–Barré syndrome in ten steps. Nature reviews. 2019
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