Guillain-Barré Guillain-Barré Syndrome Syndrome

Mohamed Sulaiman Al-Mohamed Sulaiman Al-HouqaniHouqani

A 17-year-old male developed flu-like symptoms, severe diarrhoea and abdominal pain 4 days after attending a dinner party at which he had eaten a chicken. Three other people who had attended the same party developed gastrointestinal symptoms. These symptoms settled within a few days. Stool cultures taken from all four individuals grew Campylobacter jejuni. About 10 days after the onset of diarrhoea, he developed diffuse aching around his shoulders and buttocks and pins and needles in his hands and feet. Over the next week the sensory changes worsened and spread to involve his arms and legs. His limbs became progressively weaker and 8 days after the onset of neurological symptoms he could not hold a cup or stand unaided. He was admitted to hospital and found to have severe symmetrical distal limb weakness and ‘glove and stocking’ sensory loss to the elbows and knees. Nerve conduction studies showed evidence of a mixed motor and sensory neuropathy and examination of his cerebrospinal fluid (CSF) showed a very high total protein level at 4g/l but without any increase in the number of cells in the CSF. High titres of IgM and IgG antibodies to Campylobacter jejuni were found in his peripheral blood.

Case 1

A diagnosis was made of the Guillain–Barré syndrome (acute inflammatory polyneuropathy) probably triggered by Campylobacter jejuni infection. He was treated with high-dose intravenous immunoglobulin but his condition deteriorated with respiratory muscle weakness and he required mechanical ventilation. His condition slowly improved and he was able to breathe spontaneously after 2 weeks. His strength and sensory symptoms slowly improved with vigorous physiotherapy but 1 year after the initial illness he still had significant weakness in his hands and feet.

A previously healthy 15-year-old black adolescent, gravida 1, para 0, at week 10 of gestation had a 10-day history of progressive weakness and paresthesia of the lower extremities. There was no history of a preceding infection or flu-like illness. The patient reported no symptoms in the upper extremities or shortness of breath. Neurologic examination revealed bilateral foot drop, with 4/5 strength of proximal muscles of the lower extremities and normal strength in the upper extremities and bulbar muscles. Sensory examination was remarkable for symmetrically decreased sense of vibration, light touch, and proprioception in the lower extremities (below the knees). Deep tendon reflexes were absent in the lower extremities and only trace reflexes were present in the upper extremities. Plantar flexor response was present bilaterally.

Case 2

Baseline vital capacity was 2.47 L (87% of predicted value for patient age). Thyroid function tests and screening for heavy metals, vitamin B12, and folate yielded normal results; erythrocyte sedimentation rate was within normal limits. Serum protein electrophoresis revealed a normal migration pattern. The patient did not consent to lumbar puncture. Motor nerve conduction studies revealed markedly increased distal latency of the peripheral nerves of upper and lower extremities, as well as unelicitable F wave of the peroneal nerves, consistent with acute demyelinating peripheral polyneuropathy. An antiñperipheral nerve antibody panel revealed mild elevation of GM1 antibodies (12; normal <10), with normal values for asialo-GM1, GD1a, and GD1b.

Pelvic ultrasonography revealed a normal intrauterine pregnancy, good correlation between size and gestational age, and a live and active fetus. After obstetric consultation, the patient had four sessions of plasmapheresis, with a calculated plasma-to-crystalloid exchange rate of 200 to 250 mL. The patient and fetus tolerated the procedure well. Progression of motor symptoms was arrested and a mild improvement was noticed immediately after the third plasma exchange session. Follow-up spirometries were normal and the patient did not require assisted ventilation. Follow-up ultrasonography did not show any signs of fetal distress. Aggressive physical therapy was begun and the patient was ambulatory on discharge from the hospital, 9 days after admission.

The patient received follow-up care at the High Risk Obstetrical Clinic and had an uneventful course until gestational week 20, when a decrease in frequency of fetal movements prompted immediate ultrasonography. Intrauterine fetal death was detected, and the patient was readmitted for an induced vaginal delivery. Failure to deliver the placenta required cervical dilation with evacuation of uterine contents and curettage.

Pathologic examination of placental tissue revealed CMV placentitis.

It has an annual incidence of 0.6 to 2.4 It has an annual incidence of 0.6 to 2.4

cases per 100,000 population and cases per 100,000 population and

occurs at all ages and in both sexes occurs at all ages and in both sexes

With the marked decline in the With the marked decline in the

incidence of polio, Guillain-Barré incidence of polio, Guillain-Barré

syndrome is now the most common syndrome is now the most common

cause of acute flaccid paralysis in cause of acute flaccid paralysis in

healthy peoplehealthy people

Guillain-Barré syndromeGuillain-Barré syndrome::

is an acute inflammatory demyelinating is an acute inflammatory demyelinating polyneuropathy characterized by progressive polyneuropathy characterized by progressive muscle weakness and areflexiamuscle weakness and areflexia

PATHOGENESIS PATHOGENESIS Peripheral nerve demyelination in Peripheral nerve demyelination in

Guillain-Barré syndrome is believed to Guillain-Barré syndrome is believed to

be immunologically mediatedbe immunologically mediated Humoral factors and cell-mediated Humoral factors and cell-mediated

immune phenomena have been immune phenomena have been

implicated in the damage of myelin implicated in the damage of myelin

and/or the myelin-producing Schwann and/or the myelin-producing Schwann

cells cells

Guillain-Barré syndrome has been Guillain-Barré syndrome has been reported to follow reported to follow – vaccinations vaccinations – epidural anesthesiaepidural anesthesia– thrombolytic agents thrombolytic agents

It has been associated with some It has been associated with some systemic processes, such as systemic processes, such as – Hodgkin's disease Hodgkin's disease – SLE SLE – Sarcoidosis, and Sarcoidosis, and – infection with infection with CampylobacterCampylobacter, Lyme , Lyme

disease, EBV, disease, EBV, CMVCMV, HSV, mycoplasma, and , HSV, mycoplasma, and recently acquired HIV infectionrecently acquired HIV infection

Campylobacter infectionCampylobacter infection

Campylobacter infection is the most commonly Campylobacter infection is the most commonly identified precipitant of Guillain-Barré identified precipitant of Guillain-Barré syndromesyndrome

A case-control study involving 103 patients A case-control study involving 103 patients with the disease found that 26% of affected with the disease found that 26% of affected individuals had evidence of recent C. jejuni individuals had evidence of recent C. jejuni infection compared with 2% of household and infection compared with 2% of household and 1% of age-matched controls 1% of age-matched controls

Seventy percent of those infected with C. Seventy percent of those infected with C. jejuni reported a diarrheal illness within 12 jejuni reported a diarrheal illness within 12 weeks before the onset of the neurologic weeks before the onset of the neurologic illness illness

The main lesions are acute inflammatory The main lesions are acute inflammatory demyelinating neuropathy and, particularly demyelinating neuropathy and, particularly in patients with Campylobacter-associated in patients with Campylobacter-associated disease, acute axonal degeneration disease, acute axonal degeneration

These changes may be caused by cross-These changes may be caused by cross-reacting antibodies to GM1 ganglioside reacting antibodies to GM1 ganglioside (present in high concentrations in (present in high concentrations in peripheral nerve myelin) formed in peripheral nerve myelin) formed in response to similar epitopes expressed by response to similar epitopes expressed by the infecting Campylobacter strain the infecting Campylobacter strain

However, mechanisms other than molecular However, mechanisms other than molecular mimicry may be associated with the mimicry may be associated with the production of antibodies to GM1 gangliosideproduction of antibodies to GM1 ganglioside

The Guillain-Barré syndrome variant The Guillain-Barré syndrome variant

known as Miller Fisher syndrome, in known as Miller Fisher syndrome, in

which the cranial nerves are affected, which the cranial nerves are affected,

is also associated with Campylobacter is also associated with Campylobacter

infection infection

In these patients cross-reacting In these patients cross-reacting

antibodies to GQ1b ganglioside, antibodies to GQ1b ganglioside,

which is present in cranial nerve which is present in cranial nerve

myelin, have been foundmyelin, have been found

CLINICAL FEATURES CLINICAL FEATURES

Two-thirds of patients develop the neurologic Two-thirds of patients develop the neurologic

symptoms 2-4 weeks after what appears to be symptoms 2-4 weeks after what appears to be

a benign respiratory or gastrointestinal a benign respiratory or gastrointestinal

infection infection

The initial symptoms are fine paresthesias in The initial symptoms are fine paresthesias in

the toes and fingertips, followed by lower the toes and fingertips, followed by lower

extremity weakness that may ascend over extremity weakness that may ascend over

hours to days to involve the arms, cranial hours to days to involve the arms, cranial

nerves, and in severe cases the muscles of nerves, and in severe cases the muscles of

respiration respiration

CLINICALCLINICAL FEATURESFEATURES

Early in the course, patients frequently complain Early in the course, patients frequently complain

of aching or sciatica-like lower back or leg painof aching or sciatica-like lower back or leg pain At some point during their illness, up to 25 At some point during their illness, up to 25

percent of patients require mechanical percent of patients require mechanical

ventilationventilation More than 90% of patients reach the nadir of More than 90% of patients reach the nadir of

their function within two to four weeks, with their function within two to four weeks, with

return of function occurring slowly over weeks to return of function occurring slowly over weeks to

months months

PhysicalPhysical ExaminationExamination

Symmetric limb weakness with diminished or Symmetric limb weakness with diminished or absent reflexes absent reflexes

Minimal loss of sensation despite paresthesiasMinimal loss of sensation despite paresthesias Signs of autonomic dysfunction are present in Signs of autonomic dysfunction are present in

50 percent of patients, including50 percent of patients, including– Cardiac dysrhythmias (asystole, Cardiac dysrhythmias (asystole,

bradycardia, sinus tachycardia, and bradycardia, sinus tachycardia, and atrial/ventricular tachyarrhythmias)atrial/ventricular tachyarrhythmias)

– Orthostatic hypotensionOrthostatic hypotension– Transient or persistent hypertensionTransient or persistent hypertension– Paralytic ileusParalytic ileus– Bladder dysfunctionBladder dysfunction– Abnormal sweatingAbnormal sweating

DIAGNOSTIC STUDIESDIAGNOSTIC STUDIES

Electrophysiologic studies are the most specific and Electrophysiologic studies are the most specific and sensitive tests for diagnosis of the disease sensitive tests for diagnosis of the disease

They demonstrate a variety of abnormalities They demonstrate a variety of abnormalities indicating evolving multifocal demyelinationindicating evolving multifocal demyelination– Slowed nerve conduction velocitiesSlowed nerve conduction velocities– Partial motor conduction blockPartial motor conduction block– Abnormal temporal dispersionAbnormal temporal dispersion– Prolonged distal latenciesProlonged distal latencies

A normal study after several days of symptoms, A normal study after several days of symptoms, makes the diagnosis of Guillain-Barré syndrome makes the diagnosis of Guillain-Barré syndrome unlikelyunlikely

DIAGNOSTIC STUDIESDIAGNOSTIC STUDIES

After the first week of symptoms, analysis of After the first week of symptoms, analysis of the cerebrospinal fluid (CSF) typically reveals the cerebrospinal fluid (CSF) typically reveals – normal pressures normal pressures – few cells (typically mononuclear) few cells (typically mononuclear) – an elevated protein conc. (greater than 50 mg/dL) an elevated protein conc. (greater than 50 mg/dL)

Early in the course (less than one week), Early in the course (less than one week), protein levels may not yet be elevated, but protein levels may not yet be elevated, but only rarely do they remain persistently normal only rarely do they remain persistently normal

If CSF pleocytosis is noted, other diseases If CSF pleocytosis is noted, other diseases associated with Guillain-Barré syndrome eg, associated with Guillain-Barré syndrome eg, HIV infection, Lyme disease, malignancy, and HIV infection, Lyme disease, malignancy, and sarcoidosis should be consideredsarcoidosis should be considered

TREATMENTTREATMENT

The main modalities of therapy for The main modalities of therapy for

Guillain-Barré syndrome include Guillain-Barré syndrome include

– Plasmapheresis and Plasmapheresis and

– Administration of intravenous immune Administration of intravenous immune

globulinglobulin

PlasmapheresisPlasmapheresis

Plasma exchange is recommended for patients Plasma exchange is recommended for patients who who – Are unable to walk unaided Are unable to walk unaided – Demonstrate worsening vital capacities Demonstrate worsening vital capacities – Require mechanical ventilationRequire mechanical ventilation– Have significant bulbar weakness Have significant bulbar weakness

As a result of the cost, risk, and discomfort to As a result of the cost, risk, and discomfort to the patient, plasma exchange is generally not the patient, plasma exchange is generally not used for ambulatory patients with mild disease used for ambulatory patients with mild disease or for patients whose symptoms are no longer or for patients whose symptoms are no longer progressing after three weeksprogressing after three weeks

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