1. Guillain-Barre Syndrome
Dr. M. Sofi MD; FRCP (London); FRCPEdin; FRCSEdin

2. Guillain-Barré syndrome
(GBS), or acute inflammatory demyelinating
polyradiculoneuropath (AIDP), describes a
heterogeneous condition with a number of
redundant variants.
The classic presentation is characterized by an acute
monophasic, non-febrile, post-infectious illness
manifesting as ascending weakness and
areflexia.
Sensory, autonomic, and brainstem abnormalities
may also be seen.

3. Guillain-Barré syndrome
Vaccination against the flu, rabies, and meningitis are also documented precipitating factors that have been reported.
The diagnosis of GBS is typically based on the presence of a progressive ascending weakness with areflexia .
To date, treatment for GBS has been aimed primarily at immuno-modulation
The pathogenesis of GBS remains unclear.
Increasing data indicate that it is an autoimmune disease, often triggered by a preceding viral or bacterial infection with organisms such as:
Campylobacter jejuni Cytomegalovirus
Epstein-Barr virus
Mycoplasma pneumoniae.

4. Guillain-Barre Syndrome: Clinical presentation
Weakness
The classic weakness is ascending and symmetrical in nature.
The LL are usually involved before the UL.
Proximal muscles involved earlier than the more distal ones.
Trunk, bulbar, and respiratory muscles can be affected as well.
Respiratory muscle weakness with SOB may be present.

5. Guillain-Barre Syndrome: Clinical presentation
Weakness
Patients may be unable to stand or walk despite reasonable strength, especially when ophthalmoparesis or impaired proprioception is present.
Weakness develops acutely and progresses over days to weeks.
Severity may range from mild weakness to complete tetraplegia with ventilatory failure.

6. Guillain-Barre Syndrome: Clinical presentation
Cranial nerve involvement
Cranial nerve involvement is observed in 45-75% of patients with GBS. Cranial nerves III-VII and IX-XII may be affected. Common complaints include:
Facial droop (may mimic Bell palsy)
Diplopias
Dysarthria
Dysphagia
Ophthalmoplegia
Pupillary disturbances
Facial and oropharyngeal weakness usually appears after the trunk and limbs are affected. The Miller-Fisher variant of GBS is unique in that this subtype begins with cranial nerve deficits.

7. Guillain-Barre Syndrome: Clinical presentation
Pain
On initial presentation, almost 50% of patients describe the pain as severe and distressing.
Pain is most severe in the shoulder girdle, back, buttocks, and thighs and may occur with even the slightest movements.
Dysesthesias are observed in about 50% of patients during the course of their illness.
Dysesthesias are described as burning, tingling, or shock like sensations and are often more prevalent in the LL than in UL.
Dysesthesias may persist indefinitely in 5-10% of patients.

8. Guillain-Barre Syndrome: Autonomic changes
Autonomic changes can include:
Tachycardia
Bradycardia
Facial flushing
Paroxysmal hypertension
Orthostatic hypotension
Anhidrosis and/or diaphoresis
Bowel and bladder dysfunction are rarely early or persistent findings.
Dysautonomia is more frequent in patients with severe weakness and respiratory failure.
Autonomic changes rarely persist in a patient with GBS.

9. Guillain-Barre Syndrome: Autonomic changes
Respiratory involvement
Upon presentation, 40% of patients have respiratory or oropharyngeal weakness. Typical complaints include the following:
Dyspnea on exertion
Shortness of breath
Difficulty swallowing
Slurred speech
Ventilatory failure with required respiratory support occurs in up to one third of patients at some time during the course of their disease.

10. Guillain-Barre Syndrome: Antecedent illness
Up to 2/3rd of patients with GBS report an antecedent illness or event 1-3 weeks prior to the onset of weakness.
URTI and gastrointestinal illnesses are the most commonly reported conditions.
Symptoms generally have resolved by the time the patient presents for the neurologic condition.
Campylobacter jejuni is the major causative organism identified and is responsible for cases of AIDP and acute motor axonal neuropathy (AMAN).

11. Guillain-Barre Syndrome: Antecedent illness
Vaccinations, surgical procedures, and trauma have been reported to trigger the development of GBS.
Vaccination with the swine flu vaccine administered in 1976 was shown to increase the risk of contracting GBS to a small, but definable, degree.
Rabies vaccine prepared from infected brain tissue also was found to have an association with GBS.
Studies of other vaccines, however, have not shown a significant relationship between these drugs and GBS or have been inconclusive

12. Guillain-Barre Syndrome: Physical Examination
Cardiac arrhythmias, including tachycardias and bradycardias, can be observed as a result of ANS involvement.
Tachypnea may be a sign of ongoing dyspnea and progressive respiratory failure.
Blood pressure lability is another common feature, with alterations between hypertension and hypotension.
Temperature may be elevated or low.
Respiratory examination may be remarkable for poor inspiratory effort or diminished breath sounds.

13. Guillain-Barre Syndrome: Physical Examination
Neurologic examination
Cranial nerve VII is observed most frequently, followed by symptoms associated with cranial nerves VI, III, XII, V, IX, and X
Ophthalmoparesis may be observed in up to 25% of patients
LL weakness usually begins first and ascends symmetrically and progressively over the first several days.
UL, trunk, facial, oropharyngeal weakness is observed to a variable extent.
Marked asymmetrical weakness calls the diagnosis of GBS into question.

14. Guillain-Barre Syndrome: Physical Examination
Neurologic examination
Papilledema secondary to elevated ICP is present rarely.
Patients may be unable to stand or walk despite reasonable strength, especially when ophthalmoparesis or impaired proprioception is present.
Despite frequent complaints of paresthesias, objective sensory changes are minimal.
A well-demarcated sensory level should not be observed in patients with GBS; such a finding calls the diagnosis of GBS into question.

15. Guillain-Barre Syndrome: Physical Examination
Neurologic examination
Reflexes are absent or reduced early in the disease course.
Hyporeflexia or areflexia of involved areas represents a major clinical finding on examination of the patient with GBS.
Pathologic reflexes, such as the Babinski sign, are absent.
Hypotonia can be observed with significant weakness.
Tonic pupils have been reported but only in severe cases.

16. Guillain-Barre Syndrome: Diagnostic Considerations
Problems to consider in the differential diagnosis of Guillain-Barré syndrome (GBS) include :
Acute myelopathy (e.g., from compression, transverse myelitis, vascular injury)
Chronic inflammatory demyelinating polyneuropathy (CIDP)
Conversion disorder/hysterical paralysis
Human immunodeficiency virus (HIV) peripheral neuropathy
Neurotoxic fish or shellfish poisoning
Paraneoplastic neuropathy
Poliomyelitis

17. Guillain-Barre Syndrome: Diagnostic Considerations
Porphyria polyneuropathy
Spinal cord compression
Spinal cord syndromes, particularly post-infection
Tick paralysis
Toxic neuropathies (e.g., arsenic, thallium, organophosphates, lead)
Vasculitic neuropathies
Vitamin deficiency (e.g., vitamin B-12, folate, thiamine)
West Nile encephalitis
Bilateral strokes
Acute cerebellar ataxia syndromes
Posterior fossa structural lesion

18. Guillain-Barre Syndrome: Differential diagnosis
Botulism
Cauda Equina and Conus Medullaris Syndromes
Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Heavy Metal Toxicity
Lyme Disease
Metabolic Myopathies
Multiple Sclerosis
Nutritional Neuropathy
Vasculitic Neuropathy

19. Guillain-Barre Syndrome: Biochemical Screening
The following should be considered:
LFT results are elevated in as many as one third of patients
A stool culture for C jejuni and a pregnancy test are also indicated
The syndrome of inappropriate antidiuretic hormone (SIADH) may occur
Biochemical screening include:
Electrolyte levels
Liver function tests (LFTs)
Creatine phosphokinase (CPK)
ESR

20. Guillain-Barre Syndrome: Biochemical Screening
Serologic studies are of limited value in the diagnosis of GBS. Assays for antibodies to the following infectious agents may be considered:
C jejuni
Cytomegalovirus (CMV)
Epstein-Barr virus (EBV)
Herpes simplex virus (HSV)
HIV
Mycoplasma pneumoniae
An increase in titers for infectious agents, such as CMV, EBV, or Mycoplasma, may help in establishing etiology for epidemiologic purposes.

21. Guillain-Barre Syndrome: Serological studies
Serum autoantibodies
Serum autoantibodies are not measured routinely in the workup of GBS, but results may be helpful in patients with questionable diagnosis or a variant of GBS.
Antibodies to glycolipids are observed in the sera of 60-70% of patients with GBS during the acute phase, with gangliosides being the major target antigens.
Specific antibodies found in GBS include:
Antibodies to GM1: Found in the sera of acute motor axonal neuropathy or acute demyelinating polyradiculoneuropathy (AIDP) variants of GBS
Elevated titers are closely associated antecedent C jejuni infections
Anti-GQ1b antibodies: GBS with ophthalmoplegia, including patients with the Miller-Fisher variant

22. Guillain-Barre Syndrome: Approach Considerations
Abnormalities in NCS that are consistent with demyelination are sensitive and represent specific findings for classic GBS.
Needle EMG may be normal in acute nerve lesions, and it may take 3-4 weeks for fibrillation to develop.
Guillain-Barré syndrome is generally diagnosed on clinical grounds.
Basic laboratory studies, such as CBCs and metabolic panels, are normal and of limited value in the workup.
EMG and NCS can be very helpful in the diagnosis.

23. Guillain-Barre Syndrome: Approach Considerations
In the acute phase, the only needle EMG abnormality may be abnormal motor recruitment, with decreased recruitment and rapid firing motor units in weak muscles.
Unfortunately, electrodiagnostic studies can be completely normal in acute GBS and a normal study does not rule GBS.
Delayed distal latencies, slowed nerve conduction velocities, temporal dispersion of waveforms, conduction block, prolonged or absent F waves, and prolonged or absent H-reflexes are all findings that support demyelination.

24. Guillain-Barre Syndrome: Approach Considerations
During the acute phase of GBS, characteristic findings on CSF analysis include albumino-cytologic dissociation, which is an elevation in CSF protein (>0.55 g/L) without an elevation in white blood cells.
The increase in CSF protein is thought to reflect the widespread inflammation of the nerve roots.
Frequent evaluations of pulmonary function parameters should be performed at bedside to monitor respiratory status and the need for ventilatory assistance.
Lumbar puncture for cerebrospinal fluid studies is recommended.

25. Guillain-Barre Syndrome Treatment & Management
Prehospital and Emergency Department Care
Prehospital care of patients with GBS requires careful attention to ABCs.
Administration of oxygen and assisted ventilation may be indicated, along with establishment of I/V access.
Emergency medical services personnel should monitor for cardiac arrhythmias and transport expeditiously.
In the emergency department (ED), continuation of ABCs, intravenous treatment, oxygen, and assisted ventilation may be indicated

26. Guillain-Barre Syndrome Treatment & Management
Prehospital and Emergency Department Care
Intubation should be performed on patients who develop any degree of respiratory failure. Clinical indicators for intubation in the ED include the following:
Hypoxia
Rapidly declining respiratory function
Poor or weak cough
Suspected aspiration

27. Guillain-Barre Syndrome: Immunotherapy
Plasma exchange carried out over a 10-day period may aid in removing auto-antibodies, immune complexes, and cytotoxic constituents from serum and has been shown to decrease recovery time by 50%.
In well-controlled clinical trials, the efficacy of IVIGs in GBS patients has been shown to equal that of plasma exchange.
IVIG treatment is easier to implement and potentially safer than plasma exchange.
Additionally, IVIG is the preferential treatment in hemodynamically unstable patients and in those unable to ambulate independently

28. Guillain-Barre Syndrome: Respiratory therapy/ Cardiac monitoring
Respiratory assistance should be considered when the expiratory vital capacity decreases to less than 18 mL/kg or when a decrease in oxygen saturation is noted (arterial PO2 < 70 mm Hg).
Tracheotomy may be required in a patient with prolonged respiratory failure, especially if mechanical ventilation is required for more than 2 weeks
Respiratory therapy
Approximately 1/3rd of patients with GBS require ventilatory support.
Serial assessment of ventilatory status is needed, including measurements of vital capacity and pulse oximetric monitoring.

29. Guillain-Barre Syndrome: Respiratory therapy/ Cardiac monitoring
Close monitoring of heart rate, blood pressure, and cardiac arrhythmias allows early detection of life-threatening situations.
Critically ill patients require continuous telemetry and close medical supervision in an ICU setting.
Antihypertensives and vasoactive drugs should be used with caution in patients with autonomic instability.
Hemodynamic changes related to autonomic dysfunction are usually transitory, and patients rarely require long-term medications to treat blood pressure or cardiac problems.

30. Guillain-Barre Syndrome: Nutrition/ Prevention of infection
Enteral or parenteral feedings are required for patients on mechanical ventilation to ensure that adequate caloric needs are met when the metabolic demand is high. Even patients who are off the ventilator may require nutritional support if dysphagia is severe.
Prevention of infection
The risk of sepsis and infection can be decreased by the use of minimal sedation, frequent physiotherapy, and mechanical ventilation with positive end-expiratory pressure where appropriate.

31. Guillain-Barre Syndrome: Nutrition/ Prevention of infection
Prevention of thromboses/pressure sores
Subcutaneous un-fractionated or LMWH and thromboguards are often used to prevent lower-extremity DVT and PE.
Prevention of pressure sores and contractures entails careful positioning, frequent postural changes, and daily range-of-motion (ROM) exercises.
Bowel and bladder management
Initial management is directed toward safe evacuation and the prevention of over-distention.
Monitoring for secondary infections, such as urinary tract infection, also is an area of concern.

32. Guillain-Barre Syndrome: Physical Therapy/Occupational Therapy
Approximately 40% of patients who are hospitalized with GBS require rehabilitation.
The goals of the therapy are to reduce functional deficits and to target impairments and disabilities resulting from GBS.
Active muscle strengthening can then be slowly introduced and may include isometric, isotonic, isokinetic, or progressive resistive exercises.
Mobility skills, such as bed mobility, transfers, and ambulation, are targeted functions
Overworking the muscles may, paradoxically, lead to increased weakness.

33. Guillain-Barre Syndrome: Physical Therapy/Occupational Therapy
Occupational therapy involved early in the rehabilitation program to promote upper body strengthening, ROM, and activities that aid functional self care.
Restorative and compensatory strategies can be used to promote functional improvements.
Energy conservation techniques and work simplification also may be helpful, especially if the patient demonstrates poor strength and endurance.
Recreational therapy assists in the patient's adjustment to disability and improves integration into the community.

34. Miller-Fisher Syndrome Symptoms
Miller Fisher syndrome (MFS) is a post-infectious, immune mediated neuropathy characterized in typical cases by the clinical triad of ophthalmoplegia, ataxia and areflexia.
MFS is considered to be a variant of the Guillain-Barré syndrome (GBS). The clinical symptoms usually develop within days and improve spontaneously or after treatment within weeks.
Some patients may have involvement of other cranial nerves (including facial and lower bulbar nerve) and paresis of neck, shoulder and arm musculature or may progress to GBS.

35. Miller-Fisher Syndrome Symptoms
More than 90% of MFS patients have serum antibodies to the gangliosides GQ1b and GT1a. These antibodies are most likely induced during antecedent infection by molecular mimicry and are pathogenic for peripheral nerves in animal bioassays.
MFS patients with severe MFS, bulbar weakness or progression to GBS may benefit from treatment with intravenous immunoglobulin or plasma exchange, although the therapeutic effects have not been studied in randomized controlled studies.

36. Chronic inflammatory demyelinating polyradiculoneuropathy CIDP)
It can be considered the chronic equivalent of acute inflammatory demyelinating polyradiculoneuropathy, the most common form of Guillain-Barré syndrome.
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronically progressive or relapsing symmetric sensorimotor disorder with cyto-albuminologic dissociation and interstitial and perivascular endoneurial infiltration by lymphocytes and macrophages.

37. Chronic inflammatory demyelinating polyradiculoneuropathy CIDP)
Symptoms reported include:
Initial limb weakness, both proximal and distal
Sensory symptoms (tingling and numbness of hands and feet)
Motor symptoms (usually predominant)
In 16% a relatively acute or subacute onset of symptoms
Symptoms of autonomic system dysfunction (eg, orthostatic dizziness)
CIDP starts insidiously and evolves slowly, in either a slowly progressive or a relapsing manner, with partial or complete recovery between recurrences.
Periods of worsening and improvement usually last weeks or months.
Most experts consider the necessary duration of symptoms to be greater than 8 weeks for the diagnosis of CIDP to be made.

38. CIDP
Pertinent physical findings are limited to the nervous system, except when the condition is associated with other diseases. Such findings may include the following.
Signs of cranial nerve (CN) involvement (eg, facial muscle paralysis or diplopia)
Gait abnormalities
Motor deficits (eg, symmetric weakness of both proximal and distal muscles in upper and lower extremities)
Diminished or absent deep tendon reflexes
Sensory deficits (typically in stocking-glove distribution)
Impaired coordination

39. CIDP: Diagnosis Laboratory studies include: CSF nalysis:
Elevated protein levels are common (80% of patients); 10% of patients also have mild lymphocytic pleocytosis and increased gamma globulin. Routine tests include:
CBC/ESR/ANA
Biochemistry profile
Serum and urine immunoelectrophoresis
In certain instances, genetic testing
Other tests and procedures that may be warranted are:
MRI of the spine with gadolinium enhancement
Electromyography (EMG) is a critical test to determine whether the disorder is truly a peripheral neuropathy and whether the neuropathy is demyelinating.

40. CIDP: Management Principles of treatment are:
CIDP must be treated to prevent accumulating disability that necessitates physical and occupational therapy, orthotic devices, and long-term treatment
Close follow-up care is necessary to adjust treatment
Surgical and orthopedic consultation may be required for sural nerve biopsy or in severe disease with joint deformities
Consultation with a neurologist is warranted
Consultation with a physical medicine and rehabilitation specialist is appropriate for physical and occupational therapy and evaluation for orthotic devices
Other consultations may be necessary if associated diseases are present
Physical therapy and an active lifestyle should be encouraged

41. First-line treatment for CIDP nowadays is intravenous immunoglobulin 
(IVIG) and other treatments include 
corticosteroids, 
plasmapheresis 
(plasma exchange) and which may be prescribed alone or in combination with an immunosuppressant drug.

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