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PLASMA PHARESIS IN
NEUROLOGICAL
DISORDERS
Dr. Sunil Kumar Sharma
Senior Resident
Moderator
Dr. Vijay Sardana
Sr. Professor And HOD
Dept. Of Neurology
GMC Kota
Outline
– Introduction
– Principles and Procedure
– Complications
– Indications
– Contraindications
– Guidelines and recommendations
– Conclusion
Terminology
– Apheresis (Greek aphairesis–withdrawal)- An
umbrella term for "taking away" a blood
component.
– Plasmapheresis : Automated, selective
removal of plasma by centrifugation.
– Plasma exchange [TPE]- Removal of patient
plasma and replacement with another fluid (eg,
donor plasma, colloid, crystalloid).
Terminology…
– Hemapheresis (also called cytapheresis) –
Selective removal of abnormal blood cells or
excessive numbers of cells.
– Dialysis – A diffusion-based treatment best suited
for the removal of fluid or small molecules (eg,
uremic toxins, some drugs) from the blood using
a filter.
– Plasma filtration – A technique that separates
plasma from cellular components with a highly
permeable filter (plasma filter) using a dialysis or
hemofiltration machine.
Principles and Procedure
– The aim of plasma exchange is to significantly reduce
circulating pathologic substances (antibodies) from the
plasma.
– Substance to be removed must have a sufficiently long
half life.
– Substance to be removed must acutly toxic and
resistent to conventional therapy.
TECHNIQUES
– Centrifugal cell separators
– Membrane plasma filtration
Plasma pharesis in neurological disorders
Plasma pharesis in neurological disorders
Plasma pharesis in neurological disorders
Centrifugal devices
– There is no upper limit to
the molecular weight of
proteins removed by this
method.
– Circuits are single use and
disposable.
– Platelet can decrease by as
much as 50%.
Membrane plasma filtration
– All immunoglobulins will
cross the membrane
however, some large
immune complexes and
cryoglobulins may not be
adequately cleared.
– Reuse of plasma ilters is not
advised, but performance
data do not indicate a
major loss of function
during routine plasma
exchange.
– There is no loss of platelets
– Estimate plasma volume (in liters) = 0.07 x
weight (kg) x (1 - hematocrit) .
– Usually 1-1.5 TPV or 30-40 ml/Kg of plasma is
removed/ cycle and replacement with plasma
expanders like albumin or FFP.
– 3-5 alt. day cycle.
Choice of Replacement
solution-Albumin
Advantage:
1. No risk of hepatitis/HIV
2. Stored at room
temperature
3. Allergic reaction are rare
4. No concern about ABO
blood group
5. Depletes inflammation
mediators
Disadvantage:
1. Expensive
2. No coagulation
factors
3. No
immunoglobulin's
Choice of Replacement solution-
FFP
Advantage:
1. Coagulation factors
2. Immunoglobulin‘s
Disadvantage:
1. Risk of hepatitis,
HIV transmission
2. Allergic reaction
3. Hemolytic reaction
4. ABO
incompatibility
5. Citrate load
– There is no consensus on the ideal replacement
solution during PE.
– The use of albumin and cross matching plasma
have been recommended*.
– Colloid replacement can be achieved with the
use of fresh-frozen plasma, albumin, albumin
and saline, or albumin and plasma expander
solutions.*
Korach JM, Berger P, Giraud C, Le Perff-Desman C, Chillet P. Role of replacement fluids in the immediate complications of plasma exchange. French Registry
Cooperative Group. Intensive Care Med 1998;24:452-8.
Clark WF, Rock GA, Buskard N, Shumak KH, LeBlond P, Anderson D, et al. Therapeutic plasma exchange: An update from the Canadian Apheresis Group.
Immunoadsorption technique
– In addition to PE, the immunoadsorption technique
represents a newer approach that allows a more
selective removal of circulating antibodies.
– By binding to a ligand, removal of immunoglobulin
fractions can be achieved.
– After adsorption, the cellular blood components and
plasma are combined and reinfused.
Weinstein R. Therapeutic apheresis in neurological disorders. J Clin Apher 2000;15:74-128.
Complications
Kaplan AA. American Journal of Kidney Diseases, 2008.
Indications
– AIDP/GBS
– CIDP
– MG
– Polyneuropathy associated with paraproteinemia.
– PANDAS
– LEMS
– MS
– NMOSD
– SREAT
– NMDA R Autoimmune encephalopathy
Contraindications
– Active infection
– Hemodynamic unstability
– Allergy to fresh frozen plasma or albumin .
– Allergic to Heparin
– Hypocalcemia
Plasmapheresis;Updated: Aug 29, 2016 Author: Elliot Stieglitz, MD; Chief Editor: Emmanuel C Besa, MD
Update: Plasmapheresis in
Neurologic Disorders
AAN-2011
AAN Level of
Recommendations
A = Established as effective, ineffective or harmful.
B = Probably effective, ineffective or harmful.
C = Possibly effective, ineffective or harmful.
U = Data inadequate or conflicting; given current
knowledge, treatment (test, predictor) is unproven.
– Note that recommendations can be positive or
negative.
Methods
– MEDLINE, Cochrane Library, Web of Science,
and EMBASE
– 1995 to September 2009
– A secondary bibliography search of all full-text
articles
– Relevant, fully published, peer-reviewed articles
– Search terms
– “plasmapheresis”
– “neurologic disease (exploded)”
– key text words and index words for
plasmapheresis, plasma exchange,
immunoadsorption, and double filtration
plasmapheresis
Methods...
– At least two authors reviewed each article for
inclusion.
– Strength of practice recommendations were linked
directly to levels of evidence (Levels A, B, C, and
U).
– Conflicts of interest were disclosed.
Literature Review
2263 abstracts
and 59 articles
Inclusion criteria:
- Articles reporting results from
controlled clinical trials in humans
- Abstracts available in English
Exclusion criteria:
- Articles that were not controlled
clinical trials
- Abstracts in languages other than
English
Clinical Questions
1. What is the efficacy of plasmapheresis in the
treatment of AIDP, also known as GBS?
2. What is the efficacy of plasmapheresis in the
treatment of CIDP?
2. What is the efficacy of plasmapheresis in the
treatment of dysimmune neuropathies?
3. What is the efficacy of plasmapheresis in the
treatment of MG?
Clinical Questions…
5. What is the efficacy of plasmapheresis in the
treatment of CNS demyelinating disease?
6. What is the efficacy of plasmapheresis in the
treatment of PANDAS?
7. What is the efficacy of plasmapheresis in the
treatment of Sydenham chorea?
Update: Plasmapheresis in
Neurologic Disorders-AAN 2011
Plasma pharesis in neurological disorders
Plasma pharesis in neurological disorders
Guidelines on the Use of Therapeutic
Apheresis in Clinical Practice
Evidence-Based Approach
American Society for Apheresis
June 2016
ASFA Categories
ASFA Category I indications for
therapeutic plasma exchange
– AIDP/ Guillain–Barré syndrome
– Chronic inflammatory demyelinating
polyneuropathy
– Myasthenia gravis
– Polyneuropathy associated with
paraproteinaemias
– N-methyl D-aspartate receptor antibody
encephalitis(2016)
ASFA Category II indications for
therapeutic plasma exchange
– ADEM
– Lambert–Eaton myasthenic syndrome
– Multiple sclerosis (Acute exacerbation)
– Neuromyelitis optica(acute)
– PANDAS
– Hashimoto’s encephalopathy: SREAT(2016)
ASFA Category III indications for
therapeutic plasma exchange
– Paraneoplastic neurological syndromes
– Chronic progressive Multiple sclerosis
– NMOSD-maintainance
ASFA Category IV indications for
therapeutic plasma exchange
– Amyotrophic lateral sclerosis
– Inclusion body myositis
– POEMS syndrome
Some common neurological diseases
and ASFA guideline for TPE
AIDP/GBS
– Primary treatment TPE- Category I
– TPE After IVIG –category III
– In GBS – There are autoantibodies against
various gangliosides including GM1, GD1a,
GalNAc-GD1a, GD1b, GQ1b, GD3, and GT1a,
particularly in AMAN and Miller Fisher
syndrome subtypes.
AIDP/GBS…
– The Cochrane Neuromuscular Disease Group review
of TPE in AIDP (2012)- found that TPE is most
effective when initiated within 7 days of disease onset.
– Evidence-based guidelines of the AAN –TPE=IVIG in
the treatment of GBS (Winters, 2011).
– Volume treated: 1–1.5 TPV, Frequency: Every other
day, Replacement fluid: Albumin
– Exchange 200–250 mL of plasma /kg body weight
over 10–14 days.
CIDP
– Recommendation Category-I
– Volume treated: 1–1.5 TPV
– Frequency: 2–3/week until improvement, then
taper as tolerated
– Replacement fluid: Albumin
– TPE provides short-term benefit but rapid
deterioration may occur afterwards
– The frequency of maintenance TPE may range
from weekly to monthly .
HASHIMOTO’S
ENCEPHALOPATHY; SREAT
– High dose steroid is first line Rx.
– Recommendation Category-II
– Volume treated: 1–1.5 TPV
– Frequency: Daily to every other day
– Replacement fluid: Albumin
– 3–9 procedures, mostly commonly 5.
MULTIPLE SCLEROSIS
– Acute CNS inflammatory demyelinating –Cat. II
– Chronic progressive MS , TPE – Cat. III
– Standard treatment for MS exacerbation – High
dose IV MPS.
– If unresponsive, a second steroid pulse is given
after an interval of 10–14 days.
MULTIPLE SCLEROSIS…
– In acute, severe attacks of MS in patients who
fail initial treatment with high-dose steroids, TPE
may be beneficial (Gwathmey,2014).
– TPE has also been used for drug removal in MS
patients treated with Natalizumab who developed
PML.
MS…
– Volume treated: 1–1.5 TPV
– Frequency: Acute: 5–7 over 14 days
– Chronic progressive: weekly
– Replacement fluid: Albumin
– In acute MS relapse unresponsive to steroids,
5–7 TPE procedures have a response rate of
50%.
ADEM
– Recommendation Category-II
– Indication-Steroid refractory ADEM
– High-dose IV steroids ;IV MPS 20–30
mg/kg/day (maximum 1 g/day) for 3–5 days
first-line therapy.
– It may be followed by a prolonged oral
prednisolone taper over 3–6 weeks.
ADEM…
– In one study (Llufriu, 2009) early initiation of
TPE (within 15 days of disease onset) in acute
attacks of CNS demyelination (including seven
cases of ADEM) was identified as a predictor of
clinical improvement at 6 months.
– Volume treated: 1–1.5 TPV
– Frequency Every other day
– Replacement fluid: Albumin
Llufriu S, Castillo J, Blanco Y, Ramio-Torrenta L, Rıo J, Valle`s M, Lozano M, Castella MD, Calabia J, Horga A, Graus F, Montalban X,Saiz A. Plasma exchange
for acute attacks of CNS demyelination: predictors of improvement at 6 months. Neurology 2009;73:949–953.
ADEM…
– No clear recommendations for optimal regimen .
– In one of the largest ADEM case series (Keegan,
2002), TPE achieved moderate and marked
sustained improvement in 50% of the patients.
– In the majority of studies, clinical response was
noticeable within days, usually after 2–3
exchanges.
– In published studies, TPE therapy often consisted
of 3–6 treatments.
Keegan M, Pineda AA, McClelland RL, Darby CH, Rodrigues M, Weinshenker BG. Plasma exchange for severe attacks of CNS demyelination: predictors of
response. Neurology 2002;58:143–146.
NEUROMYELITIS OPTICA
SPECTRUM DISORDERS
– Recommendation Category-
– Acute -II
– Maintenance TPE –III
– Acute attacks are managed by high-dose
intravenous steroids (usually intravenous pulse
steroids (methylprednisone 1 g daily 3- 5 days
followed by oral steroid taper) and, if
symptoms fail to resolve, TPE is added.
NMOSD…
– Volume treated: 1–1.5 TPV
Frequency:
1. Acute: Daily or every other day;
2. Maintenance: Variable
– Replacement fluid: Albumin
NMOSD…
– The majority of studies performed five
procedures on average for acute exacerbation.
– In one case series, 5 out 7 patients who were on
maintenance TPE therapy (3 per week for 2
weeks, 2 per week for 2 weeks, then weekly for
3–5 weeks) showed varying degrees of
improvement and reduction in the number of
NMOSD exacerbation
MYASTHENIA GRAVIS
– Recommendation Category
– Moderate–severe TPE –Cat. I
– Pre-thymectomy TPE –Cat. I
– Myasthenic crisis is characterized by acute
respiratory failure requiring intubation,
prolonged intubation following thymectomy, or
bulbar weakness causing dysphasia and high risk
of aspiration.
MG…
Four major treatment approaches-
1. Cholinesterase inhibitors
2. Thymectomy
3. Immunosuppression,
4. TPE or IVIG.
MG…
– TPE is used to remove circulating
autoantibodies, particularly in-
1. Myasthenic crisis
2. Perioperatively for thymectomy,
3. As an adjunct to other therapies to maintain
optimal clinical status
MG…
– IVIG and TPE appear equivalent in the literature
– Typical induction regimen consists of processing
225 mL/kg of plasma over a period of up to two
weeks but smaller volumes process can also be
beneficial.
– Number and frequency of procedures depends upon
clinical scenario.
– Some patients may require long-term maintenance
TPE.
LEMS
– Recommendation category-II
– Autoimmune disorder of presynaptic neuromuscular
transmission- anti VGCC antibody.
– Its classical clinical triad include:
1. Muscle weakness (most prominent in proximal
muscles of the lower extremities)
2. Hyporeflexia
3. Autonomic dysfunction (e.G., Dry mouth,
constipation, and male impotence).
LEMS
– In contrast to myasthenia gravis (MG), brain
stem symptoms such as diplopia and dysarthria
are uncommon.
– Associated with SCLC
– Other CA –lymphoma and malignant thymoma
– No controlled trials exist on the use of TPE in the
LEMS.
LEMS…
– In one series, 8 out 9 patients (Newsom-Davis,
1984) had increase in electromyographic muscle
action potential (P<0.01) while receiving TPE
and immunosuppression.
– 5 to 15 daily TPE over 5–19 days to 8–10 TPE
carried out at 5–7 day intervals.
– Improvement may not be seen for 2 weeks or
more after initiation of TPE.
LEMS…
– Treatment should continue until a clear clinical and
EMG response is obtained or at least until a 2–3
week course of TPE has been completed.
– Repeated courses -in case of neurological relapse,
– Effect may last only upto 6 weeks in the absence of
immunosuppressive therapy.
NMDA RECEPTOR ANTIBODY
ENCEPHALITIS
– Recommendation category-I
– An acute autoimmune neurological disorder first
described by dalmau(2007).
– It is characterized by IgG antibodies targeting the
synaptic GLuN1 (also known as NR1) subunit of
the NMDAR.
NMDA RECEPTOR
ANTIBODY ENCEPHALITIS
– 50% have an underlying neoplasm; usually
ovarian teratoma.
– Definitive diagnosis -by the detection of
NMDAR autoantibodies in the serum, and more
specifically in the CSF.
– Imaging, EEG, and brain biopsy are typically
nondiagnostic.
– Delay in diagnosis is common - often mistaken
for psychosis or viral encephalitis.
NMDA RECEPTOR
ANTIBODY ENCEPHALITIS
First-line immunotherapies-
1. IV MPS
2. IVIG, and/or TPE.
– Approximately 50% of patients respond to these
first-line immunotherapies
– Other 50% require second-line therapies-
rituximab or combination of rituximab and
cyclophosphamide
NMDA RECEPTOR
ANTIBODY ENCEPHALITIS
– 75–80% -recover or improve (50% within 4 weeks
of treatment)
– 20%- substantial deficits or death.
– Relapses -12–20%
– Disease activity appears to correlate with antibody
levels.
NMDA RECEPTOR
ANTIBODY ENCEPHALITIS
– Dalmau (2011) proposed a treatment plan consisting
of teratoma removal (if present), corticosteroids
and/or IVIG and/or TPE (alone or any combination)
as the first-line of treatment), and rituximab and
cyclophosphamide as the second-line of treatment
for non-responders.
– The exact order of the treatments (corticosteroids,
IVIG, and TPE) was not defined.
NMDA RECEPTOR
ANTIBODY ENCEPHALITIS
– Furthermore, systematic comparisons between
the three first-line modalities are unavailable
(Titulaer, 2013).
– Recent case series (Pham, 2011; DeSena, 2015)
suggest early initiation of TPE or TPE followed
by IVIG provide better outcomes
– 5–6 TPE procedures on alternate days.
Conclusion
– Removal of immunoglobulins
– Centrifugation and Plasma filtration
– Albumin MC used
– 5 cycles alt. days
– Good response in GBS,Myasthenia crisis,
Autoimmune encephalitis.
– Good for acute management
Plasma pharesis in neurological disorders
References
– Joseph Schwartz et al; Guidelines on the Use of Therapeutic
Apheresis in Clinical Practice—Evidence-Based Approach from
the Writing Committee of the American Society for Apheresis:
The Seventh Special Issue ;.; Journal of Clinical Apheresis
31:149–338 (2016)
– Update: Plasmapheresis in Neurologic Disorders; Report of the
Therapeutics and Technology Assessment Subcommittee of the
American Academy of Neurology; Irene Cortese, MD et al; 2011.
– American Academy of Neurology (AAN) guideline update
(Neurology ® 2011;2011;76:294–300) regarding use of
plasmapheresis in treating neurologic disorders
– Neurology in clinical practice ;Bradley 7TH edition.

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Plasma pharesis in neurological disorders

  • 1. PLASMA PHARESIS IN NEUROLOGICAL DISORDERS Dr. Sunil Kumar Sharma Senior Resident Moderator Dr. Vijay Sardana Sr. Professor And HOD Dept. Of Neurology GMC Kota
  • 2. Outline – Introduction – Principles and Procedure – Complications – Indications – Contraindications – Guidelines and recommendations – Conclusion
  • 3. Terminology – Apheresis (Greek aphairesis–withdrawal)- An umbrella term for "taking away" a blood component. – Plasmapheresis : Automated, selective removal of plasma by centrifugation. – Plasma exchange [TPE]- Removal of patient plasma and replacement with another fluid (eg, donor plasma, colloid, crystalloid).
  • 4. Terminology… – Hemapheresis (also called cytapheresis) – Selective removal of abnormal blood cells or excessive numbers of cells. – Dialysis – A diffusion-based treatment best suited for the removal of fluid or small molecules (eg, uremic toxins, some drugs) from the blood using a filter. – Plasma filtration – A technique that separates plasma from cellular components with a highly permeable filter (plasma filter) using a dialysis or hemofiltration machine.
  • 5. Principles and Procedure – The aim of plasma exchange is to significantly reduce circulating pathologic substances (antibodies) from the plasma. – Substance to be removed must have a sufficiently long half life. – Substance to be removed must acutly toxic and resistent to conventional therapy.
  • 6. TECHNIQUES – Centrifugal cell separators – Membrane plasma filtration
  • 10. Centrifugal devices – There is no upper limit to the molecular weight of proteins removed by this method. – Circuits are single use and disposable. – Platelet can decrease by as much as 50%. Membrane plasma filtration – All immunoglobulins will cross the membrane however, some large immune complexes and cryoglobulins may not be adequately cleared. – Reuse of plasma ilters is not advised, but performance data do not indicate a major loss of function during routine plasma exchange. – There is no loss of platelets
  • 11. – Estimate plasma volume (in liters) = 0.07 x weight (kg) x (1 - hematocrit) . – Usually 1-1.5 TPV or 30-40 ml/Kg of plasma is removed/ cycle and replacement with plasma expanders like albumin or FFP. – 3-5 alt. day cycle.
  • 12. Choice of Replacement solution-Albumin Advantage: 1. No risk of hepatitis/HIV 2. Stored at room temperature 3. Allergic reaction are rare 4. No concern about ABO blood group 5. Depletes inflammation mediators Disadvantage: 1. Expensive 2. No coagulation factors 3. No immunoglobulin's
  • 13. Choice of Replacement solution- FFP Advantage: 1. Coagulation factors 2. Immunoglobulin‘s Disadvantage: 1. Risk of hepatitis, HIV transmission 2. Allergic reaction 3. Hemolytic reaction 4. ABO incompatibility 5. Citrate load
  • 14. – There is no consensus on the ideal replacement solution during PE. – The use of albumin and cross matching plasma have been recommended*. – Colloid replacement can be achieved with the use of fresh-frozen plasma, albumin, albumin and saline, or albumin and plasma expander solutions.* Korach JM, Berger P, Giraud C, Le Perff-Desman C, Chillet P. Role of replacement fluids in the immediate complications of plasma exchange. French Registry Cooperative Group. Intensive Care Med 1998;24:452-8. Clark WF, Rock GA, Buskard N, Shumak KH, LeBlond P, Anderson D, et al. Therapeutic plasma exchange: An update from the Canadian Apheresis Group.
  • 15. Immunoadsorption technique – In addition to PE, the immunoadsorption technique represents a newer approach that allows a more selective removal of circulating antibodies. – By binding to a ligand, removal of immunoglobulin fractions can be achieved. – After adsorption, the cellular blood components and plasma are combined and reinfused. Weinstein R. Therapeutic apheresis in neurological disorders. J Clin Apher 2000;15:74-128.
  • 16. Complications Kaplan AA. American Journal of Kidney Diseases, 2008.
  • 17. Indications – AIDP/GBS – CIDP – MG – Polyneuropathy associated with paraproteinemia. – PANDAS – LEMS – MS – NMOSD – SREAT – NMDA R Autoimmune encephalopathy
  • 18. Contraindications – Active infection – Hemodynamic unstability – Allergy to fresh frozen plasma or albumin . – Allergic to Heparin – Hypocalcemia Plasmapheresis;Updated: Aug 29, 2016 Author: Elliot Stieglitz, MD; Chief Editor: Emmanuel C Besa, MD
  • 20. AAN Level of Recommendations A = Established as effective, ineffective or harmful. B = Probably effective, ineffective or harmful. C = Possibly effective, ineffective or harmful. U = Data inadequate or conflicting; given current knowledge, treatment (test, predictor) is unproven. – Note that recommendations can be positive or negative.
  • 21. Methods – MEDLINE, Cochrane Library, Web of Science, and EMBASE – 1995 to September 2009 – A secondary bibliography search of all full-text articles – Relevant, fully published, peer-reviewed articles – Search terms – “plasmapheresis” – “neurologic disease (exploded)” – key text words and index words for plasmapheresis, plasma exchange, immunoadsorption, and double filtration plasmapheresis
  • 22. Methods... – At least two authors reviewed each article for inclusion. – Strength of practice recommendations were linked directly to levels of evidence (Levels A, B, C, and U). – Conflicts of interest were disclosed.
  • 23. Literature Review 2263 abstracts and 59 articles Inclusion criteria: - Articles reporting results from controlled clinical trials in humans - Abstracts available in English Exclusion criteria: - Articles that were not controlled clinical trials - Abstracts in languages other than English
  • 24. Clinical Questions 1. What is the efficacy of plasmapheresis in the treatment of AIDP, also known as GBS? 2. What is the efficacy of plasmapheresis in the treatment of CIDP? 2. What is the efficacy of plasmapheresis in the treatment of dysimmune neuropathies? 3. What is the efficacy of plasmapheresis in the treatment of MG?
  • 25. Clinical Questions… 5. What is the efficacy of plasmapheresis in the treatment of CNS demyelinating disease? 6. What is the efficacy of plasmapheresis in the treatment of PANDAS? 7. What is the efficacy of plasmapheresis in the treatment of Sydenham chorea?
  • 29. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice Evidence-Based Approach American Society for Apheresis June 2016
  • 31. ASFA Category I indications for therapeutic plasma exchange – AIDP/ Guillain–Barré syndrome – Chronic inflammatory demyelinating polyneuropathy – Myasthenia gravis – Polyneuropathy associated with paraproteinaemias – N-methyl D-aspartate receptor antibody encephalitis(2016)
  • 32. ASFA Category II indications for therapeutic plasma exchange – ADEM – Lambert–Eaton myasthenic syndrome – Multiple sclerosis (Acute exacerbation) – Neuromyelitis optica(acute) – PANDAS – Hashimoto’s encephalopathy: SREAT(2016)
  • 33. ASFA Category III indications for therapeutic plasma exchange – Paraneoplastic neurological syndromes – Chronic progressive Multiple sclerosis – NMOSD-maintainance
  • 34. ASFA Category IV indications for therapeutic plasma exchange – Amyotrophic lateral sclerosis – Inclusion body myositis – POEMS syndrome
  • 35. Some common neurological diseases and ASFA guideline for TPE
  • 36. AIDP/GBS – Primary treatment TPE- Category I – TPE After IVIG –category III – In GBS – There are autoantibodies against various gangliosides including GM1, GD1a, GalNAc-GD1a, GD1b, GQ1b, GD3, and GT1a, particularly in AMAN and Miller Fisher syndrome subtypes.
  • 37. AIDP/GBS… – The Cochrane Neuromuscular Disease Group review of TPE in AIDP (2012)- found that TPE is most effective when initiated within 7 days of disease onset. – Evidence-based guidelines of the AAN –TPE=IVIG in the treatment of GBS (Winters, 2011). – Volume treated: 1–1.5 TPV, Frequency: Every other day, Replacement fluid: Albumin – Exchange 200–250 mL of plasma /kg body weight over 10–14 days.
  • 38. CIDP – Recommendation Category-I – Volume treated: 1–1.5 TPV – Frequency: 2–3/week until improvement, then taper as tolerated – Replacement fluid: Albumin – TPE provides short-term benefit but rapid deterioration may occur afterwards – The frequency of maintenance TPE may range from weekly to monthly .
  • 39. HASHIMOTO’S ENCEPHALOPATHY; SREAT – High dose steroid is first line Rx. – Recommendation Category-II – Volume treated: 1–1.5 TPV – Frequency: Daily to every other day – Replacement fluid: Albumin – 3–9 procedures, mostly commonly 5.
  • 40. MULTIPLE SCLEROSIS – Acute CNS inflammatory demyelinating –Cat. II – Chronic progressive MS , TPE – Cat. III – Standard treatment for MS exacerbation – High dose IV MPS. – If unresponsive, a second steroid pulse is given after an interval of 10–14 days.
  • 41. MULTIPLE SCLEROSIS… – In acute, severe attacks of MS in patients who fail initial treatment with high-dose steroids, TPE may be beneficial (Gwathmey,2014). – TPE has also been used for drug removal in MS patients treated with Natalizumab who developed PML.
  • 42. MS… – Volume treated: 1–1.5 TPV – Frequency: Acute: 5–7 over 14 days – Chronic progressive: weekly – Replacement fluid: Albumin – In acute MS relapse unresponsive to steroids, 5–7 TPE procedures have a response rate of 50%.
  • 43. ADEM – Recommendation Category-II – Indication-Steroid refractory ADEM – High-dose IV steroids ;IV MPS 20–30 mg/kg/day (maximum 1 g/day) for 3–5 days first-line therapy. – It may be followed by a prolonged oral prednisolone taper over 3–6 weeks.
  • 44. ADEM… – In one study (Llufriu, 2009) early initiation of TPE (within 15 days of disease onset) in acute attacks of CNS demyelination (including seven cases of ADEM) was identified as a predictor of clinical improvement at 6 months. – Volume treated: 1–1.5 TPV – Frequency Every other day – Replacement fluid: Albumin Llufriu S, Castillo J, Blanco Y, Ramio-Torrenta L, Rıo J, Valle`s M, Lozano M, Castella MD, Calabia J, Horga A, Graus F, Montalban X,Saiz A. Plasma exchange for acute attacks of CNS demyelination: predictors of improvement at 6 months. Neurology 2009;73:949–953.
  • 45. ADEM… – No clear recommendations for optimal regimen . – In one of the largest ADEM case series (Keegan, 2002), TPE achieved moderate and marked sustained improvement in 50% of the patients. – In the majority of studies, clinical response was noticeable within days, usually after 2–3 exchanges. – In published studies, TPE therapy often consisted of 3–6 treatments. Keegan M, Pineda AA, McClelland RL, Darby CH, Rodrigues M, Weinshenker BG. Plasma exchange for severe attacks of CNS demyelination: predictors of response. Neurology 2002;58:143–146.
  • 46. NEUROMYELITIS OPTICA SPECTRUM DISORDERS – Recommendation Category- – Acute -II – Maintenance TPE –III – Acute attacks are managed by high-dose intravenous steroids (usually intravenous pulse steroids (methylprednisone 1 g daily 3- 5 days followed by oral steroid taper) and, if symptoms fail to resolve, TPE is added.
  • 47. NMOSD… – Volume treated: 1–1.5 TPV Frequency: 1. Acute: Daily or every other day; 2. Maintenance: Variable – Replacement fluid: Albumin
  • 48. NMOSD… – The majority of studies performed five procedures on average for acute exacerbation. – In one case series, 5 out 7 patients who were on maintenance TPE therapy (3 per week for 2 weeks, 2 per week for 2 weeks, then weekly for 3–5 weeks) showed varying degrees of improvement and reduction in the number of NMOSD exacerbation
  • 49. MYASTHENIA GRAVIS – Recommendation Category – Moderate–severe TPE –Cat. I – Pre-thymectomy TPE –Cat. I – Myasthenic crisis is characterized by acute respiratory failure requiring intubation, prolonged intubation following thymectomy, or bulbar weakness causing dysphasia and high risk of aspiration.
  • 50. MG… Four major treatment approaches- 1. Cholinesterase inhibitors 2. Thymectomy 3. Immunosuppression, 4. TPE or IVIG.
  • 51. MG… – TPE is used to remove circulating autoantibodies, particularly in- 1. Myasthenic crisis 2. Perioperatively for thymectomy, 3. As an adjunct to other therapies to maintain optimal clinical status
  • 52. MG… – IVIG and TPE appear equivalent in the literature – Typical induction regimen consists of processing 225 mL/kg of plasma over a period of up to two weeks but smaller volumes process can also be beneficial. – Number and frequency of procedures depends upon clinical scenario. – Some patients may require long-term maintenance TPE.
  • 53. LEMS – Recommendation category-II – Autoimmune disorder of presynaptic neuromuscular transmission- anti VGCC antibody. – Its classical clinical triad include: 1. Muscle weakness (most prominent in proximal muscles of the lower extremities) 2. Hyporeflexia 3. Autonomic dysfunction (e.G., Dry mouth, constipation, and male impotence).
  • 54. LEMS – In contrast to myasthenia gravis (MG), brain stem symptoms such as diplopia and dysarthria are uncommon. – Associated with SCLC – Other CA –lymphoma and malignant thymoma – No controlled trials exist on the use of TPE in the LEMS.
  • 55. LEMS… – In one series, 8 out 9 patients (Newsom-Davis, 1984) had increase in electromyographic muscle action potential (P<0.01) while receiving TPE and immunosuppression. – 5 to 15 daily TPE over 5–19 days to 8–10 TPE carried out at 5–7 day intervals. – Improvement may not be seen for 2 weeks or more after initiation of TPE.
  • 56. LEMS… – Treatment should continue until a clear clinical and EMG response is obtained or at least until a 2–3 week course of TPE has been completed. – Repeated courses -in case of neurological relapse, – Effect may last only upto 6 weeks in the absence of immunosuppressive therapy.
  • 57. NMDA RECEPTOR ANTIBODY ENCEPHALITIS – Recommendation category-I – An acute autoimmune neurological disorder first described by dalmau(2007). – It is characterized by IgG antibodies targeting the synaptic GLuN1 (also known as NR1) subunit of the NMDAR.
  • 58. NMDA RECEPTOR ANTIBODY ENCEPHALITIS – 50% have an underlying neoplasm; usually ovarian teratoma. – Definitive diagnosis -by the detection of NMDAR autoantibodies in the serum, and more specifically in the CSF. – Imaging, EEG, and brain biopsy are typically nondiagnostic. – Delay in diagnosis is common - often mistaken for psychosis or viral encephalitis.
  • 59. NMDA RECEPTOR ANTIBODY ENCEPHALITIS First-line immunotherapies- 1. IV MPS 2. IVIG, and/or TPE. – Approximately 50% of patients respond to these first-line immunotherapies – Other 50% require second-line therapies- rituximab or combination of rituximab and cyclophosphamide
  • 60. NMDA RECEPTOR ANTIBODY ENCEPHALITIS – 75–80% -recover or improve (50% within 4 weeks of treatment) – 20%- substantial deficits or death. – Relapses -12–20% – Disease activity appears to correlate with antibody levels.
  • 61. NMDA RECEPTOR ANTIBODY ENCEPHALITIS – Dalmau (2011) proposed a treatment plan consisting of teratoma removal (if present), corticosteroids and/or IVIG and/or TPE (alone or any combination) as the first-line of treatment), and rituximab and cyclophosphamide as the second-line of treatment for non-responders. – The exact order of the treatments (corticosteroids, IVIG, and TPE) was not defined.
  • 62. NMDA RECEPTOR ANTIBODY ENCEPHALITIS – Furthermore, systematic comparisons between the three first-line modalities are unavailable (Titulaer, 2013). – Recent case series (Pham, 2011; DeSena, 2015) suggest early initiation of TPE or TPE followed by IVIG provide better outcomes – 5–6 TPE procedures on alternate days.
  • 63. Conclusion – Removal of immunoglobulins – Centrifugation and Plasma filtration – Albumin MC used – 5 cycles alt. days – Good response in GBS,Myasthenia crisis, Autoimmune encephalitis. – Good for acute management
  • 65. References – Joseph Schwartz et al; Guidelines on the Use of Therapeutic Apheresis in Clinical Practice—Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Seventh Special Issue ;.; Journal of Clinical Apheresis 31:149–338 (2016) – Update: Plasmapheresis in Neurologic Disorders; Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology; Irene Cortese, MD et al; 2011. – American Academy of Neurology (AAN) guideline update (Neurology ® 2011;2011;76:294–300) regarding use of plasmapheresis in treating neurologic disorders – Neurology in clinical practice ;Bradley 7TH edition.