​Kembara Xtra - Medication - Guillain Barre Syndrome

​Kembara Xtra - Medication - Guillain Barre Syndrome 
Introduction 

 A class of inherited autoimmune diseases characterized by ascending paralysis that gets worse over the course of up to four weeks and acute peripheral neuropathy

Subtypes organized according to brain damage pattern:
- In approximately 95% of GBS cases in Europe and North America, increasing limb weakness with areflexia is caused by acute inflammatory demyelinating polyradiculoneuropathy (AIDP).
- Subtypes of axons:
Acute motor axonal neuropathy (AMAN) is a type of pure motor neuropathy that is firmly linked to Campylobacter jejuni and is associated with a greater incidence of respiratory failure (5% of cases in Europe and North America, compared to 30-47% of cases in China, Japan, and Central and South America).
The combined motor-sensory neuropathy known as acute motor-sensory axonal neuropathy (AMSAN) has a poor prognosis and a protracted course.
– Subtypes by region:
Miller Fisher syndrome (MFS): triad of ophthalmoplegia, ataxia, and areflexia; 90% of MFS patients have antibodies to GQ1b
Bickerstaff encephalitis, which has encephalopathy, ophthalmoplegia, ataxia, and hyperreflexia, is thought to be a variety of MFS.
Pharyngeal-cervical-brachial GBS causes upper extremity areflexia, neck, arm, and oropharyngeal paralysis as a result of parasympathetic and cholinergic dysfunction.
- Subtypes of senses:
Orthostatic hypotension, gastroparesis, ileus, constipation/diarrhea, sudomotor/pupillary abnormalities, and neuropathic pain are also symptoms of acute pandysautonomia.
A contentious variation with sensory loss and ataxia is known as acute sensory ataxic neuropathy (ASAN).
Polyneuritis cranialis: bilateral involvement of cranial nerves and severe peripheral sensory loss linked to CMV infections
GBS, AIDP, acute inflammatory idiopathic polyneuritis, acute autoimmune neuropathy, Landry ascending paralysis are all synonyms for the condition.


Caution 
Twenty to thirty percent of individuals experience rapidly advancing paralysis and respiratory failure. Within 48 hours, some people need mechanical ventilation.
Areflexia in patients with quickly progressing limb weakness is a warning sign for GBS. GBS is suggested by a history of weakness accompanied by a GI or respiratory infection.

Epidemiology Incidence: Most prevalent acute paralytic disease in Western nations; incidence in the United States ranges from 0.9 to 1.8/100,000; increases with age: 0.8/100,000 in children under the age of 18; 3/100,000 in people over the age of 60; 1.5 times greater incidence in males

Pathophysiology and Etiology 

Peripheral nerve damage and demyelination are caused by a post-infectious autoimmune response that attacks the Schwann cell surface membrane, myelin, and/or gangliosides.
Molecular mimicry, or an immune reaction to antigenic targets that coincidentally share properties of infectious organisms and host peripheral nerve tissue, is hypothesized to play a role in pathogenesis. When antibodies cross-react with GM1 myelin ganglioside, the peripheral nervous system is damaged.

Genetics
There is no apparent hereditary risk associated with GBS, but host factors appear to be involved.

Risk Elements 
A systematic review study on the COVID-19 vaccine found that the Pfizer, Johnson & Johnson, and Sinovac coronavirus vaccines had a GBS rate of 1.8 to 53 cases per 1 million doses.
Influenza vaccinations — Inactivated seasonal flu vaccines linked to an increase in GBS risk equal to one case/million immunizations above background incidence (far lower than the 17 cases of GBS per million influenza virus-infected individuals).
- There was no increase in the 2017–2018 flu season in the incidence of GBS linked to the flu vaccine. Historical significance: The vaccine-attributable risk for increased incidence during the National H1N1 Immunization Program in 1976 was 8.8 per million receivers, compared to 1.6 per million recipients during the H1N1 vaccination campaign in 2009.

Accompanying Conditions 
Infection of the respiratory (22–53%) or gastrointestinal (GI) tract (6-26%) in the six weeks before to the onset of the GBS: Campylobacter jejuni is the most frequent cause of GBS, accounting for 21-40% of cases.
- Linked to shorter recovery, more severe residual impairment, and axonal degeneration
Rarely related with Mycoplasma pneumoniae, influenza infection, Epstein-Barr virus, varicella-zoster virus, HIV infection, zika virus, and various arboviral illnesses; primary CMV infection precedes 10–22% of cases.

Presenting History In the first week, 73% of people with AIDP achieve its functional nadir; by the end of the first month, 98% have it at its worst.
Prior respiratory or gastrointestinal infection
The earliest signs and symptoms include pain, numbness, paresthesias, or proximal muscular weakness. These symptoms might progress to affect cranial nerves and breathing muscles.
Facial nerve palsy, diplopia, dysarthria, dysphagia, and ophthalmoplegia are cranial nerve symptoms.
Purely sensory symptoms do not include GBS. Neuropathic pain, sometimes severe, occurs in 30-50% of cases, most frequently in the back and lower extremities.

clinical assessment 
Standard GBS diagnostic standards include:
Essential for diagnosis:
Affects more than one leg; progressive weakening with nadir between 12 hours and 28 days; areflexia/hyporeflexia
Strongly endorsing:
- Paresthesias that very slightly alter an objective sense of touch or pinprick (e.g.
- Relative symmetry - Involvement of the cranial nerves, including weakening of the face muscles on both sides or symmetrically
- Within 4 weeks of the progression ceasing, recovery will start - Autonomic dysfunction, including urine retention, diarrhea, and constipation, as well as tachycardia, bradycardia, face flushing, hypertension, and hypotension, will also be addressed.
- No fever at the start

Multiple Diagnoses 
Acute flaccid paralysis differential diagnosis:
Brain: brainstem encephalitis and basilar artery stroke; spinal cord: transverse myelitis and spinal cord compression
Poliomyelitis and acute flaccid myelitis affect the motor neuron.
Other peripheral neuropathies include acute intermittent porphyria, chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), vasculitis, critical illness polyneuropathy, infectious disease (such diphtheria, Lyme disease, and HIV), and critical illness polyneuropathy.
Myasthenia gravis, Eaton- Lambert syndrome, botulism, and toxins (such as heavy metals, inhalant misuse, and organophosphates) are all conditions that affect the neuromuscular junction.
Muscle: acute rhabdomyolysis, trichinosis, inflammatory myopathy, electrolyte disruption (hypokalemia, hypophosphatemia), and periodic paralysis
Weakness's psychological causes

Initial test results from the laboratory and imaging
Research to make the diagnosis:
- Lumbar puncture (LP): In 80% of instances, increased CSF protein without pleocytosis is seen (Note: CSF protein is frequently normal within the first 48 hours of symptom onset; the majority of GBS patients will have CSF protein >400 mg/L).
NCS: Nerve conduction studies The most helpful confirmatory test shows aberrant conduction velocities in 85% of patients with demyelination, even at the earliest stages of the condition. Repeat the test if nondiagnostic in a week or two.
Imaging is typically not necessary. Cauda equina and/or spinal nerve root enhancement can be seen on MRI.
Research to identify the root cause:
- Stool culture and C. jejuni serology - Acute and convalescent CMV, EBV, HIV, and M. pneumoniae serology
- Anti-GM1 antibodies in AMAN and anti-GQ1b antibodies in the MFS variation.
- Rheumatoid factor, B12/folate, hemoglobin A1C, ESR, RPR, and heavy metal assay for peripheral neuropathy


Tests in the Future & Special Considerations
Before administering intravenous immunoglobulin (IVIG), which might result in aseptic meningitis, analyze the CSF. The subtype of GBS can be identified by a repeat NCS three to eight weeks following start.

Sural nerve biopsy is not necessary unless it is done to rule out vasculitis or amyloidosis.

Management 

To prevent the disease from progressing, consider admission (respiratory function, autonomic stability, paralysis).
Supportive care is crucial, with a focus on pain control, neurogenic bladder/bowel, and immobility-related comorbidities.
NSAIDs can aid with pain management but are frequently insufficient.
In GBS patients, gabapentin and carbamazepine reduce the need for opioids. Nobody is better than anyone else.

DVT prevention is advised for nonambulatory patients.
If ileus is present, neostigmine or erythromycin may be helpful.

The First Line of Medicine
IVIG for five days at 0.4 g/kg/day or, less often, for two days at 1 g/kg/day.
- Plasma exchange (PE) and IVIG both hasten recovery in cases of severe disease when administered within two weeks of the beginning.
– IVIG speeds up healing in children as compared to supportive care alone. Combining IVIG with PE does not result in any clinically noticeable benefits.

PE: those treated with PE recover their ability to walk more quickly (NNT 7), need mechanical ventilation less frequently and for a shorter period of time (NNT 8), regain complete muscle strength more quickly (NNT 8), and experience fewer severe sequelae at one year (NNT 17) as compared to those only receiving supportive care.
– PE was found to have higher relapse chances than supportive therapy, but there was no difference in mortality or severe infection.
- Two PE sessions are preferable than none in mild GBS. Four sessions are preferable to two in mild GBS. Six sessions are not noticeably superior to four in severe GBS.
– When PE is started within 7 days of the disease's onset, it is most useful. PE is still beneficial after 30 days.
– Unknown to 12 year olds is the value of physical education.

Next Line
Corticosteroids are not helpful when used alone or in conjunction with other treatments. Low-quality data indicate that steroids slow down healing.

CSF filtration is identical to PE filtration.

Brain-derived neurotrophic factor and interferon are comparable to a placebo.

Further Treatments 
Speech and language treatment improves swallowing function, if compromised; physical and occupational therapy improves tiredness and functional ability.


Alternative Therapies 
In one short trial, tripterygium polyglycoside dramatically accelerated healing more than corticosteroids (NNT 4).


Admissions
Admit patients who appear to have GBS.

 Continuously assess vital capacity (VC) and static maximum inspiratory and expiratory pressures (PImax and PEmax) to closely monitor respiratory state.

Respiratory failure predictors include:
- Rapid progression: 3 days or less elapsed between the onset of weakness and admission to the hospital
- Bulbar and/or facial weakness - VC decline of more than 30%
- A 60-point total for the bilateral upper arm abductors, elbow flexors, wrist extensors, hip flexors, knee extensors, and foot dorsal flexors indicates muscle weakness according to the Medical Research Council (MRC) sum score.
Reasons to intubate a patient:
VC = 20 mL/kg, PI = 30 cm H2O, and PE = 40 cm H2O.
Use frequent rotation and DVT prevention to avoid problems from immobility.
Pulmonary toilet, aspiration prevention, and respiratory care
Keep an eye out for ileus and urine retention in the colon and bladder.
Start physical treatment right away to maintain passive range of motion.
Patients with mild symptoms who are stable for more than two weeks and can walk without assistance are less likely to develop disease progression and can be handled as outpatients. Keep an eye out for ileus and urine retention in the colon and bladder.


Patient Follow-Up Monitoring
Patients need close monitoring of their cardiac, respiratory, and hemodynamic functions, usually in an intensive care unit (ICU).
Pulmonary function tests (VC, respiratory frequency) every 2 to 6 hours during the advancing phase and every 12 to 16 hours during the plateau phase
Keep an eye on the bulbar sensitivity to airway secretions and weakness.
Telemetry in people with serious illnesses

Modification of Lifestyle 
Explain the stages of disease and emphasize the expectation of a significant recovery.

Three stages of sickness, if left untreated, are the prognosis:
- The most dangerous and complicated phase of the initial progressive phase lasts up to 4 weeks.
The plateau phase is variable.
- During the healing phase (weeks to months), proximal and eventually distal strength are regained.

The majority of recovery happens in the first year.
80% of patients recover between 6 to 12 months, with a maximum of 18 months since commencement.
After a year, 20–39% of people still have a disability:
- Musculoskeletal discomfort, sensory ataxia, intrinsic hand muscle atrophy, tiredness, and bilateral footdrop - Half of these with severe handicap

Age >60 years, rapid progression, severe disease, severe disability upon admission or release, prior diarrhea, male sex, positive C. jejuni or CMV serology, axonal degeneration, and need for mechanical ventilation are factors associated with poor functional outcome.


Complications 
3-7% mortality in North America and Europe. Patients over age 65 and those with advanced disease are most at risk.
Approximately 20–30% need mechanical ventilation.
Approximately 70% of people experience autonomic dysfunction along with hemodynamic instability, urine retention, ileus, and anhidrosis.
10% of people relapsed.
2% of people get relapsing CIDP.

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