Guillain-Barré syndrome (GBS) was named after two French doctors who first described a number of cases of acute ascending muscular weakness ⁶. It is an acute immune-mediated disorder associated with inflammation and demyelination of the cranial and spinal nerves, characterised by a rapid progressive ascending muscle weakness resulting in varying degrees of motor dysfunction⁴^,⁶^,⁷. The syndrome occurs in children and adults, and is the most common cause of acute neuromuscular paralysis in developed countries⁸^,⁹. There appear to be two major peaks of occurrence, in young adults and in persons aged over 55 years ¹⁰^,¹¹. Although it can be fatal, prompt diagnosis and good management of symptoms leads to recovery of 80–90% of patients, with few or no remaining disabilities⁷^,⁸.

Case study

Sandra Probona, 23, presented complaining of a three-day history of mild weakness in her lower limbs, ‘feeling funny’ in her legs, and a recent tendency to trip when walking. She said that about two weeks ago, she had had the ‘flu’ with a runny nose and a cough and had felt cold. As it was the weekend, she had not seen a doctor, and had treated it with over-the-counter medication and rest, and had felt able to go to work by the Monday.

On examination, she had abnormal gait with loss of plantar flexion, and a marked decrease in her ability to dorsiflex, invert and evert her feet. She had loss of sensation to deep pressure in her feet and decreased deep tendon reflexes at the ankle and knee. The strength in her quadriceps was reduced with a score of 3/5. Further examination demonstrated loss of position sense below mid-calf, and slight reduction in her ability to discriminate between temperature extremes and between sharp and blunt objects. Sensation, movement and strength were normal in her trunk and arms. No speech or swallowing deficits, breathing difficulties or cardiac arrythmias were present at this time. A diagnosis of Guillain-Barré syndrome was made following diagnostic tests that excluded other possible diagnoses.

Following admission, Sandra was monitored for progression of the paralysis, cardiac irregularities and respiratory function. Progression of her symptoms continued with loss of quadriceps strength and tendon reflexes. Cardiac monitoring showed sinus rhythm; her respiratory rate and depth, vital capacity and pulse oximetry remained within normal limits. Treatment with intravenous immunoglobulin was commenced and the physiotherapist consulted for assessment for splinting of her paralysed legs. Nerve conduction studies performed 10 days after admission showed reduced response in the peroneal and tibial nerves.

WHAT IS THE PATHOPHYSIOLOGY?

GBS is believed to be caused by a cell-mediated autoimmune attack on the myelin surrounding the cranial and spinal nerves in response to a virus. Of patients with GBS, 50% have reported a viral-like illness 10–14 days prior to onset of symptoms ⁷^,¹². Haemophilus influenzae, Mycoplasma pneumonia, Epstein-Barr virus, HIV and Camyplobacter jejuni infection have all been linked to GBS, as have patients who are immunocompromised, such as those who have AIDS or are post-organ transplant¹²^–¹⁴.

In GBS, it is believed that an immunologic reaction results in inflammation and oedema of the myelin sheath of the nerve axon and the anterior and posterior nerve roots of the spinal nerve. In response, lymphocytes and macrophages move in to the area, which results in patchy loss of myelin (demyelination) from the affected peripheral nerves and wider spaces between the nodes of Ranvier. The more highly myelinated motor, and some cranial, nerves are affected more than those responsible for cutaneous pain, touch and temperature. In some cases, there may be injury to the axon itself ⁴^,⁶^,¹¹.

Demyelination causes impaired transmission of electrical impulses along the affected nerves due to the inability of the action potential to travel down the neuron and reach the target organ (loss of saltatory conduction). The result is a decrease in or loss of function in the organs the affected nerves innervate. The degree of dysfunction the patient experiences depends upon the degree of demyelination in the affected nerves. In motor nerves, muscle weakness and a flaccid paralysis (areflexia) can occur. Similarly, disruption of the posterior sensory nerve roots results in paresthesia, numbness, tingling and burning sensations, while the consequence of disruption to the autonomic nervous system may be a labile blood pressure and cardiac arrythmias ⁴^,⁶^,¹¹.

There is a range of variants of GBS based on the degree of peripheral nerve involvement or the site of inflammation, but ascending GBS or acute motor-sensory axonal neuropathy is the most common type, with symmetrical weakness and numbness starting in the legs and progressing to the trunk, arms and cranial nerves. Respiratory function is affected in 50% of cases ⁸. Other variants are descending GBS, pure motor GBS or acute motor axonal neuropathy in which there is no sensory loss; and Miller-Fisher, a rare type, more common in China, Japan, Africa, and South America, which results in ophthalmoplegia, areflexia and ataxia⁸.

WHAT ARE THE CLINICAL MANIFESTATIONS?

The presenting signs and symptoms depend upon the degree of peripheral nerve involvement and the severity of the demyelination. Characteristically, the person will present with a progressive symmetrical ascending weakness of skeletal muscles. The weakness usually starts in the legs and may then affect the trunk, arms, and cranial nerves, with reduction in or loss of tendon reflexes ⁸^–¹⁴. In severe cases, respiratory failure may occur if the nerves supplying the intercostal muscles and diaphragm or the 10th cranial (vagus) nerve are affected. If the cranial nerves are involved, clinical signs will depend upon the nerve affected. For example, if the facial nerve is affected, there will be difficulty in smiling, frowning, or drinking with a straw. Dysphagia and paralysis of the larynx can occur due to involvement of the 9th, 10th, 11th and 12th cranial nerves⁸.

If there is sensory involvement, then paresthesia, sensations of tingling, altered sensation to touch and numbness in the extremities, reduced proprioception and sensory loss in a ‘stocking and glove’ distribution may be present. Pain and muscle stiffness in the limbs and back are also reported in about 25% of patients, and may become severe ⁸.

Rapid shallow breathing with the use of the accessory muscles of respiration (abdominal, intercostal muscles, shoulder girdle) is present as the intercostal muscles and diaphragm become weaker. If vital capacity falls below 15mL/kg, there is a risk of respiratory failure and mechanical ventilation is indicated as alveolar hypoventilation and respiratory acidosis develop ⁸^,¹⁵. The most serious complication, respiratory failure requiring admission to ICU and mechanical ventilation, occurs in approximately 20–35% of cases¹⁶.

Autonomic dysfunction results in hypotension, hypertension or a labile blood pressure, and tachycardia, bradycardia or cardiac arrhythmias. Paralytic ileus, urinary retention, and inappropriate antidiuretic hormone secretion can also occur ⁸^,⁹.

GBS has three phases: acute, plateau and recovery. Symptoms usually occur 10–14 days following a viral infection and reach their peak in the third or fourth week. However in some cases, respiratory failure occurs within 48 hours of the onset of symptoms ¹⁰^,¹⁵. The acute phase lasts 1–3 weeks and begins when the first obvious symptoms develop, ending when no further symptoms appear or deterioration has ceased. The plateau phase, during which no change or improvement occurs, lasts from days to two weeks, while recovery time when remyelination and regrowth of axons occur can last from four months to three years. Approximately 80% of people recover from most effects by one year, although a 3% relapse rate has been reported after complete or near recovery ⁹^,¹⁵.

WHAT SHOULD YOU BE LOOKING AT IN LABORATORY AND OTHER TESTS?

The diagnosis is based on medical history and assessment of the level of motor, sensory or autonomic involvement. A full assessment of motor and sensory (touch, proprioception, temperature) function, deep tendon and plantar reflexes, cranial nerves, respiratory effort and spirometry is required. Although a number of laboratory tests can be carried out, most will not show any change in the initial stages of the disease.

Lumbar puncture and examination of the CSF will demonstrate an increase in protein over several days, peaking 4–6 weeks after onset of the disease, normal white cell count and some increase in CSF pressure. Blood tests may show an elevated erythrocyte sedimentation rate (ESR) and raised levels of immunoglobulin can be measured in the serum. Electromyography (EMG) and nerve conduction studies will demonstrate a slowing of the velocity of nerve conduction to voluntary muscle as demyelination occurs ⁸^,¹³.

WHAT IS THE TREATMENT?

GBS is potentially reversible in the majority of cases if it is detected early. The primary goals of treatment are to modify the course of the disease, provide supportive management related to the signs and symptoms, and prevent complications; and this requires a multidisciplinary team approach.

Immunomodulation therapy has been found to prevent further progression of the disease and reduce recovery time if instigated within the first two weeks of the disease ⁹. Indications for immunomodulation therapy are rapid progression of the disease, bulbar involvement, respiratory dysfunction, and/or loss of mobility. Intravenous immunoglobulin (IVIg) is the most commonly used treatment, as it is less invasive than plasmapheresis and is usually given over 2–5 days for a total dose based on body weight⁸. Plasmapheresis aims to remove circulating antimyelin antibodies, and a daily exchange of plasma is performed over 4–5 days¹⁷. However, it has been reported as less useful for the treatment of children, a proportion of who may have poorer long-term outcomes¹⁸^–²⁰.

APPLIED PHARMACOLOGY

Pharmacological management is based on immunomodulation therapy, prevention of complications and treatment of signs and symptoms. Anticoagulant therapy (heparin)²¹ is administered to prevent deep venous thrombosis and pulmonary embolus, both complications related to reduced venous return due to the flaccid paralysis and loss of normal muscle pump activity. Analgesia will be required if muscle pain is present and may include narcotics. Autonomic system manifestations, such as cardiac arrhythmias, bradycardia, and hypotension, may require appropriate medication to treat these symptoms. Neuromuscular blocking agents are to be avoided due to the risk of prolonging muscle paralysis.

NURSING IMPLICATIONS

Monitoring to detect signs of ascending paralysis and sensory loss are paramount. In particular, observing for poor airway clearance, respiratory failure, poor swallowing, and autonomic complications is essential to provide early treatment. Further, in determining the progress of the disease and preventing complications, assessment of motor and sensory function, pain, respiratory patterns, vital capacity, swallowing, cardiac rate and rhythm, blood pressure and urinary output are all important. Nursing interventions to prevent secondary complications, such as superimposed respiratory and urinary infection, limb contractures, bowel and bladder dysfunction, pressure ulcers, muscle atrophy, thrombo-embolic episodes and inadequate nutrition, are essential if the patient is to recover with minimal side effects. Psychological support, communication and education for both patients and their families are important to reduce anxiety and fear of the possible outcome.

In any patient diagnosed with Guillain-Barré syndrome, it is important that frequent and accurate monitoring of motor and sensory, respiratory and autonomic function is carried out to evaluate the progression of the disease and the need for prompt intervention of supportive therapy if respiratory failure or cardiac involvement occurs. In this case study, the disease progression following admission affected the motor function in Sandra’s lower limbs and did not progress further to involve her trunk muscles or arms. This, in conjunction with prompt diagnosis and commencement of a five-day course of immunomodulation therapy, meant that she was transferred to a rehabilitation unit 17 days following admission. Electromyography confirmed that demyelination was present. She received intensive inpatient rehabilitation for a period of 4 months and continued to receive physiotherapy on an outpatient basis for a further 7 months. At this time she appeared to have made a full recovery, with no residual motor or sensory deficits.

MULTIPLE SCLEROSIS

WHAT DOES IT MEAN?

Multiple sclerosis (MS) is unpredictable inflammation, demyelination and scarring of the myelin in the brain, spinal cord and cranial nerves, resulting in widespread neurologic dysfunction. It is characterised by remissions and exacerbations of varying severity, with some patients having a rapidly progressive disease; however the majority (70%) have prolonged remissions ²².

The incidence of disease is more common in people of northern European descent, in women born in the northern hemisphere from urban and high socioeconomic backgrounds, and there is often a family history ⁸. Multiple sclerosis is a major cause of disability in people between 18–40 years, with average age at onset being 30 years⁸.

There is no one identified cause of MS and environmental agents, a slow acting virus, autoimmune response, allergic response, anoxia, toxins, and nutritional, traumatic and genetic factors have all been considered. The risk of developing the disease decreases in people who migrate from a high-risk area before adolescence, leading to a hypothesis that an environmental agent may trigger an autoimmune response in genetically susceptible people. An increase in humoral and cell-mediated T and B cells has been identified in the plaque ²².

Case study

Gilda Swensson, 32, an accountant, presented to her general practitioner four months ago complaining of ‘fuzzy’ vision. This resolved with no further problems until recently, when the fuzziness returned, accompanied by double vision. At the last visit she complained of weakness in her legs and a tendency for her right foot ‘to trip her up’. Her general practitioner referred her to a neurologist for further investigation.

During her assessment, she said she had migrated from northern Europe with her family when she was 18 years of age. On examination, she had 75% of normal muscle strength in her right lower leg and 60% in her left leg. Examination of her gait showed mild right foot drop and slight knee hyperextension. A visual evoked potential test demonstrated a decrease in her visual sensory conduction time. An appointment for an MRI was to be made, and she was referred to physiotherapy for assessment.

WHAT IS THE PATHOPHYSIOLOGY?

There is sporadic patchy demyelination of the white matter of the central nervous system in brain, spinal cord and cranial nerves, with a preference for the optic nerves, brain stem, cerebellum and spinal cord white matter secondary to inflammation ⁴. Scarring from proliferation of the glial cells (gliosis) of the myelin sheath occurs in the affected areas with hard yellow plaques replacing the myelin. This scar tissue damages the axon fibre and causes disruption of the conduction of nerve impulses, usually in the brain, spinal cord or optic nerves. Nerve impulses may be slowed, blocked or be abnormal or ectopic, and this disruption accounts for the variation in symptoms with which patients present⁸.

Remission, with an improvement in symptoms, is thought to occur when the inflammation ceases or the lesions heal, with impulse transmission returning as remyelination by the oligodendrocytes occurs. Residual disability may be due to only part remyelination of lesions occurring. Symptoms become irreversible if further lesions develop, with permanent myelin loss and axonal loss if the disease progresses ⁶^,²³.

Classification of multiple sclerosis is based upon the timing of exacerbations and disease progression, with remissions varying from months to years and relapses lasting days to months ²³^,²⁴ (see Table 8.1).

TABLE 8.1 TYPES AND CHARACTERISTICS OF VARIANTS OF MULTIPLE SCLEROSIS

Type	Characteristics
Relapsing-remitting MS (RRMS) Most common	Recurrent episodes of neurological dysfunction with full, incomplete or no recovery. No progression of symptoms between attacks. 80% of cases are stable between attacks
Secondary progressive MS (SPMS)	Begins as RRMS but the number of attacks reduces and is replaced by a steady deterioration unrelated to attacks after twenty years or more
Primary progressive MS (PPMS) 10–15%	Older age onset. Characterised by a progressive course from the beginning signs and symptoms with no acute attack
Progressive relapsing MS (PRMS) 5%	Progressive deterioration from first symptoms, with an occasional acute attack

WHAT ARE THE CLINICAL MANIFESTATIONS?

Clinical manifestations vary depending on the extent and location of demyelination, and therefore the varying presentations and unpredictable progress of the disease can make diagnosis difficult. The most common initial manifestations are visual and sensory alterations. Blurred vision and pain in the eye (optic neuritis), diplopia (double vision) and/or sensory disturbances, such as paresthesia, numbness and tingling, loss of balance, decreased ability to distinguish temperature and proprioception, are most commonly reported ²⁴.

Other signs and symptoms include emotional lability due to involvement of white matter in the frontal lobes. Gait ataxia, problems with balance and coordination, tremor, slurred speech and nystagmus occurs due to involvement of the cerebellum. Brain stem lesions affect swallowing and speech, while muscle weakness and spasticity are related to spinal cord tract involvement, as are bladder, bowel and sexual dysfunction ²⁴.

Approximately 65% of patients will have some form of cognitive impairment affecting functions such as memory, attention, information processing, executive function and visual spatial skills ²⁵. These are independent of disease progression and are often undiagnosed or mistaken for depression.

The onset of an attack may be preceded by stress or an upper respiratory tract infection, and as the disease progresses, heat sensitivity and fatigue exacerbate the symptoms.

WHAT SHOULD YOU BE LOOKING AT IN LABORATORY AND OTHER TESTS?

There is no single test that diagnoses MS and initially, testing may not demonstrate any specific findings consistent with the disease. A negative test result does not rule out the diagnosis of multiple sclerosis, as it is based on the total picture rather than a single test ²³. Diagnosis is based on past and present patient history, full neurological examination including cranial nerves, motor, sensory and cerebellar function, and mental status. Magnetic resonance imaging (MRI) is the most sensitive test for multiple sclerosis, although CT scanning may show lesions in the white matter. MRI shows the size, number and location of lesions in the white matter brain or spinal cord in about 95% of cases. Evoked potential testing demonstrates slowed absent or abnormal conduction pathways of visual, auditory, sensory or motor nerve impulses in 85% of people²³.

Components of the breakdown of myelin are released into the CSF as demyelination occurs and these components can be measured by three tests. The CSF IgG (immunoglobulin G) Index test detects IgG synthesis if the ratio of IgG: albumen is greater than the serum ratio. The normal IgG index is 0.77 or less, and the normal ratios of IgG: albumin in CSF is 0.15–0.38 and 0.15–0.41 in serum. The oligoclonal band test is used to examine if synthesis of immunoglobulin G (IgG) has occurred and is positive in more than 90% of patients with multiple sclerosis ⁸. The third test, the CSF myelin basic protein test, is positive if elevated above 4ng/mL. However, as elevated levels occur in other demyelinating disorders, CNS trauma or infection, it cannot be used as the only test²⁶.

Diagnosis is based on age, signs and symptoms of disease of the brain or spinal cord following neurological examination, evidence of 2 or more lesions on an MRI scan and a history of two or more episodes lasting at least 24 hours and occurring at least one month apart, or progressive development of signs and symptoms over at least 6 months with no other cause or explanation ⁸^,²⁶.