Diabetic neuropathy

2. • Acute Onset
• Usually Monophasic
• Immune mediated disorder
• Peripheral Nervous System

3. GBS = AIDP
New Concept
Other Variants

4. • First described by Landry in 1859.
• Recognized as GBS since 1916, when Guillain, Barre´,
and Strohl described two French soldiers who contracted
the illness during World War I.

5. • Incidence Rate : 1–2 / 100,000 population.
• The lifetime likelihood of any individual acquiring GBS is
1:1000.
• In Europe and North America : AIDP(90% of the cases).
• In China and Japan : AMAN(most common).

7. • A peak incidence between June–July and Sept–October.
• Western countries - GBS is common in 5th decade.
• India - more common at a younger age.
• Equally common in men and women.

8. • Often follows an upper or lower respiratory illness or
gastroenteritis by 10 to 14 days.
• Approximately 70% of patients can identify a preceding
illness.
• Infections associated with GBS - CMV, M. pneumoniae,
EBV, Influenza A, H. influenzae, Enterovirus,
Campylobacter jejuni and Zika virus.

9. • Cytomegalovirus : most common associated virus.
• Campylobacter jejuni : most frequently associated
bacterial infection.(overall 40%)
• Other less common precipitants are surgery, pregnancy,
cancer, and vaccinations.

10. • Evolves over days, often beginning with numbness in the
lower limbs and weakness in the same distribution.
• Approximately 50% of patients achieve maximum
weakness by 2 weeks, 80% by 3 weeks, and 90% by 4
weeks.
• Progression beyond 4 weeks is unusual.
• Neuropathic pain - 66% patients(localized to the lower
back and thighs).

11. • The weakness begins distally and spreads proximally.
• In rare cases, the weakness may be localized to the legs
only (giving the appearance of paraplegia).
• Sensory examination : normal or show minor
deficiencies in vibration and proprioception.
• All patients have areflexia or at least hyporeflexia at
some time in the illness.

12. • 50% of patients - some degree of facial weakness.
• Weakness attributed to cranial nerves includes ocular
dysmotility, pupillary changes, and ptosis.
• Ophthalmoparesis : approximately 20% of patients with
GBS.

13. • 30% of patients develop respiratory failure from phrenic
nerve disease, requiring intubation and ventilation.
• Autonomic involvement : tachycardia, bradycardia,
hypertension and hypotension, gastric hypomotility, and
urinary retention.

15. • An axonal motor variant of GBS
• Reported in 1993 from Northern China
• So K/As Chinese paralytic illness.
• Can present with transient conduction block without
axonal loss and this led to the term acute motor
conduction block neuropathy.

16. • More common in children during the summer.
• Pure motor without sensory symptoms and signs.
• NCS – decreased CMAP amplitudes, normal latencies
and conduction velocities, and normal sensory studies.

17. • Sensory involvement also occurs
• Later age of onset
• Broader geographic distribution
• A more protracted course
• Slower and incomplete improvement

18. • Acute or subacute demyelinating
polyradiculoneuropathy.
• Clinical presentation differs markedly from typical AIDP.
• Triad of ophthalmoplegia, areflexia, and ataxia.
• Often grouped with Bickerstaff brainstem encephalitis -
similar presentation plus encephalopathy and
corticospinal tract dysfunction.

19. • The prognosis in both Miller Fisher syndrome and
Bickerstaff brainstem encephalitis is favorable.
• Most patients improve within 1 to 2 months and make a
complete recovery in 6 months even without specific
treatment.

20. • Rare
• Sympathetic and parasympathetic nervous systems
involved.
• CVS involvement, Blurry vision, anhydrosis.
• Recovery is often gradual and incomplete.
• Often combined with sensory features.

21. • Molecular mimicry plays a major role.
• Molecular mimicry is believed to occur where the
immune system recognizes the myelin epitope as
‘‘foreign’’ and targets it for destruction.

26. • Elevated CSF protein - may not be present until 3 weeks
after the onset of the illness.
• Pleocytosis (greater than 5 white blood cells) - not
present in patients with GBS
• 15% of patients -10 to 50 cells per high-power field.
• If a pleocytosis is present, it raises suspicion for an
infectious process; sarcoidosis; or carcinomatous or
lymphomatous meningitis.

28. • In first few days – NCS may be normal or only show
subtle changes of demyelination, such as prolonged or
absent F waves and H reflexes, and patchy changes in
distal latencies in patients with AIDP.
• As the disease evolves - conduction block, temporal
dispersion, and prolonged distal and F-wave latencies.

29. • Sensory NCS - A characteristic sural nerve sparing.
• Sensitivity of NCS - As low as 22% in early AIDP and
rise to 87% at 5 weeks.
• A conduction velocity of <70% of the lower limit of
normal and a distal latency of >150% of the upper limit of
normal was highly sensitive and had a specificity of
nearly 100% for AIDP.

30. • Needle EMG - Decreased recruitment initially, followed
by fibrillation potentials over weeks 2 to 5 in proximal
and distal muscles simultaneously.

31. • The best electrodiagnostic indicator for a rapid or good
recovery is maintained motor amplitude.
• Patients with an average amplitude >10% of the lower
limit of normal likely have a major component of
conduction block which has the potential to reverse.
• Amplitudes <10% during illness are seen in patients with
a greater degree of axonal injury and a more prolonged
recovery.

32. • To assess for gadolinium enhancement of nerve roots.
• To eliminate other causes of quadriparesis, particularly
transverse myelitis, subacute compressive myelopathy,
and infiltrating illnesses of the roots and the spinal cord.
• 95% of children with GBS show enhancement of the
lumbar roots secondary to the inflammatory process.

40. • (1) time from GBS onset to hospital admission of less
than seven days
• (2) inability to lift the elbows or head above the bed
• (3) inability to stand
• (4) ineffective coughing

42. • Plasma exchange
• IVIg
• Corticosteroids(not approved)

43. • First treatment shown to be effective.
• Removes autoantibodies, immune complexes,
complement, and cytokines.
• Boosts T-cell suppressor function.
• Dose - 250 mL/kg divided over 5 alternating days.
• Risks - central venous catheter placement, hypotension,
cardiac arrhythmia, vasovagal spell, allergic reaction to
albumin replacement, hypocalcemia, anemia, and
thrombocytopenia.

44. 2017

45. Patients with mild GBS on admission should receive 2
PEs. Patients with moderate and severe forms should
benefit from 2 further exchanges.

46. • Pooled IgG from thousands of blood donors, which
results in a fivefold increase in serum IgG.
• Adverse events - mild infusion-related symptoms
(nausea and headache), aseptic meningitis, rash, severe
rare anaphylaxis, and, in fewer than 2% of cases, renal
failure.
• IVIg may be preferred since it is easier to administer.

47. IVIg is as effective as plasma
exchange.
NEJM 1992

48. Lancet 1997

49. 2016

51. • PE is recommended for nonambulant patients within 4
weeks of onset (level A, class II evidence) and for
ambulant patients within 2 weeks of onset (level B,
limited class II evidence).
• The effects of PE and IV immunoglobulin (IVIg) are
equivalent.
• There is insufficient evidence to recommend the use of
CSF filtration (level U, limited class II evidence).

52. • The evidence is insufficient to recommend the use of
immunoabsorption (level U recommendation, class IV
evidence).
• IVIg is recommended for patients with GBS who require
aid to walk within 2 (level A recommendation) or 4 weeks
from the onset of neuropathic symptoms (level B
recommendation derived from class II evidence
concerning PE started within the first 4 weeks and class I
evidence concerning the comparisons between PE and
IVIg started within the first 2 weeks).

53. • The effects of IVIg and PE are equivalent.
• Corticosteroids are not recommended for the treatment
of patients with GBS (level A, class I evidence).
• PE and IVIg are treatment options for children with
severe GBS (level B recommendation derived from class
II evidence in adults).

55. • Inhibition of complement using eculizumab prevents
neuropathy in an animal model of Miller Fisher
syndrome.
• Limitations - significant cost and potential complications,
including a high risk of meningococcal infections.
• Other complement inhibitors - APT070, rEV576,
nafamostat mesylate, and soluble complement receptor
1 have been evaluated in animal models.

56. • One possible strategy for axon protection is sodium
channel blockade.
• Supporting this approach are data indicating flecainide
protects axons in an animal model (experimental
autoimmune neuritis [EAN]).
• Another general approach to axon protection, or
enhanced regeneration, is growth factor therapy.

57. • The voltage gated potassium antagonist, 4
aminopyridine represents a potential approach for GBS
patients with residual gait dysfunction.

58. • Treatment-related fluctuations are defined as worsening
of weakness after an initial improvement or after
stabilization following treatment with IVIg or plasma
exchange.
• Occur in approximately 10% of patients with GBS.
• Usually take place within the first 2 months after
treatment.
• Treated with another course of IVIg or plasma exchange,
and the treatment is often beneficial.

59. • If the patient experiences more than one treatment-
related fluctuation, and particularly if it occurs 2 months
or more after the onset of the illness, then the diagnosis
of CIDP becomes a strong consideration.

60. • The prognosis for most patients with GBS is for good to
excellent recovery.
• Approximately 87% experience full recovery or minor
deficits.
• Most of the improvement in GBS occurs within the first
year, but patients may continue to improve for up to 3
years or longer.

61. • Mortality in GBS is 3% to 7%
• Most often attributable to respiratory failure, infection, or
uncontrollable autonomic dysfunction.

64. • New variants
• Diagnostic and prognostic criteria have come
• Newer treatment modalities under trials

66. • Guillain-Barre´ Syndrome. P D Donofrio. Continuum
2017;23(5):1295–1309.
• Acquired Immune Demyelinating Neuropathies. M M
Dimachkie. Continuum 2014;20(5):1241–1260.
• Immune-Mediated Neuropathies. Y T So. Continuum
Lifelong Learning Neurol 2012;18(1):85–105.
• Guillain-Barré Syndrome. X A Londono et al. Semin
Neurol 2012;32:179–186.
• Inflammatory Neuropathies. J Whitesell. Semin Neurol
2010;30(4):356-364.