Question

List the pharmacological interventions for Acute inflammatory demyelinating polyradiculopathy also known as Guillain-Barre syndrome, and state the category the drug belongs as well as the actions and side effects

Answer 1

Guillain–Barré syndrome (GBS) is an acute onset, usually monophasic immune-mediated disorder of the peripheral nervous system. The term GBS is often considered to be synonymous with acute inflammatory demyelinating polyradiculoneuropathy (AIDP), but with the increasing recognition of variants over the past few decades, the number of diseases that fall under the rubric GBS have grown to include axonal variants and more restricted variants, such as Miller Fisher syndrome

Guillain–Barré syndrome—clinical variants

Epidemiology

The reported incidence rates for GBS are 1–2 per 100,000 population.[2–4] The lifetime likelihood of any individual acquiring GBS is 1:1000.[5] The subtypes of GBS have different incidence rates in different parts of the world. In Europe and North America AIDP is dominant contributing to 90% of the cases. In contrast in China and Japan AMAN being the most common subtype.[6,7] The picture is intermediate when we look at other population. In Indian series the incidence of AIDP and AMAN are virtually equal although AMAN is more common in younger patients.[8] There seems to be a slight preponderance of AIDP in studies by Gupta et al[9] and by Meena et al (unpublished data from NIMS, Hyderabad). Available Indian literature indicates a peak incidence between June–July and Sept–October.[10] In western countries, GBS is common in the 5th decade,[11] but in India it occurs more commonly at a younger age.[10,12] GBS is equally common in men and women and can occur at any age. There is a male preponderance among the hospitalized population.

Clinical Features

Most often an unremarkable infection, such as upper respiratory infection, often predates the onset of GBS by 14 days.[2,5] Many antecedent infections have been identified, including Campylobacter jejuni, cytomegalovirus (CMV), Mycoplasma pneumonia, Epstein–Barr virus, influenza virus, JEV.[13,14] Surgery, immunization, and parturition have also been associated with GBS. GBS usually begins abruptly with distal, relatively symmetrical onset of paraesthesias and quickly followed by progressive limb weakness. Progression is rapid, with 50% of patients reaching clinical nadir by 2 weeks and more than 90% by 4 weeks. The current diagnostic criteria include <4 weeks of progression to clinical nadir. Approximately 80%–90% of patients with GBS become nonambulatory during the illness.[15,16] Pain is prominent in 50% of patients.[16,17] Neurological examination is characterized by distal and often proximal, relatively symmetrical, weakness. Although GBS is essentially a motor neuropathy, sensory dysfunction is seen in a few patients. It is seen more in a demyelinating form of GBS.[12,18] Sensory examination is often normal in the early phase of disease. Facial or pharyngeal weakness is commonly seen in GBS. Diaphragmatic weakness due to phrenic nerve involvement is also common. Approximately one third of hospitalized GBS patients require mechanical ventilation due to respiratory muscle or oropharyngeal weakness.[18,19] Tachycardia is common but more serious autonomic nervous system dysfunction may occur, including life-threatening arrhythmias, hypotension, hypertension, and gastrointestinal dysmotility. The incidence is between 27% and 55% and is more common in demyelinating than axonal form.

Pathogenesis

Major advances have been made in understanding the mechanisms of some of the subtypes. The histological appearance of the AIDP subtype resembles experimental autoimmune neuritis, which is predominantly caused by T cells directed against peptides from the myelin proteins P0, P2, and PMP22. The role of T-cell-mediated immunity in AIDP remains unclear and there is evidence for the involvement of antibodies and complement. Strong evidence now exists that axonal subtypes of Guillain–Barré syndrome, acute motor axonal neuropathy (AMAN), and acute motor and sensory axonal neuropathy (AMSAN), are caused by antibodies to gangliosides on the axolemma that target macrophages to invade the axon at the node of Ranvier. About a quarter of patients with Guillain–Barré syndrome have had a recent C. jejuni infection, and axonal forms of the disease are especially common in these people. The lipo-oligosaccharide from the C. jejuni bacterial wall contains ganglioside-like structures and its injection into rabbits induces a neuropathy that resembles acute motor axonal neuropathy.[21–23] Antibodies to GM1, GM1b, GD1a, and GalNac-GD1a are in particular implicated in acute motor axonal neuropathy and, with the exception of GalNacGD1a, in acute motor and sensory axonal neuropathy.

Diagnosis

Progressive weakness in both upper and lower extremities within 4 weeks along with areflexia is essential requirement for the diagnosis. Supportive ancillary testing for GBS includes CSF analysis and electrodiagnostic testing, both of which may be normal in the early phase of GBS. The limitations of ancillary testing in the early phase combined with the importance of prompt treatment of GBS mandates that the clinician at times make the diagnosis based solely on history and examination. An elevated CSF protein concentration (with normal cell count) is only found on initial CSF analysis in 50% of patients; elevated CSF protein concentration occurs in more than 90% of patients at the peak of the disease. CSF pleocytosis is an important red flag, which raises the question of infectious (HIV, CMV, Lyme, sarcoid), carcinomatous, or lymphomatous polyradiculoneuropathy

Guillian–Barré syndrome—red fl ags raising other diagnostic possibilities

Electrodiagnosis

Electrodiagnostic (EDX) testing is performed to support the clinical impression. EDX testing of GBS patients often demonstrates features of demyelination, such as temporal dispersion, significantly slow conduction velocities, and prolonged distal and F-wave latencies.[24] Electrodiagnostic testing features of acquired demyelination (eg, conduction block, temporal dispersion, nonuniform slowing of conduction velocities) are particularly helpful because these findings are characteristic of immune-mediated demyelinating neuropathies. In early GBS, prolonged distal compound muscle action potential (CMAP) latencies and temporal dispersion are more commonly demonstrated than are slow motor conduction velocities and conduction block.[27] Another electrodiagnostic testing hallmark of GBS is the “sural sparing” pattern; that is, the finding of a normal sural sensory nerve response in the setting of abnormal upper extremity sensory nerve results.[27] This pattern is very unusual for neuropathies other than GBS. Sural sparing, a marker of demyelinating neuropathy, is more commonly seen in later than in early stages of AIDP. Other electrodiagnostic testing abnormalities are frequently encountered in early GBS but they are less specific to GBS. These include absent H-reflexes, low motor nerve CMAP amplitudes on distal stimulation, and prolonged F-wave responses.[25–27] It is reported that the H-reflex was absent in 97% of GBS patients within the first week of symptom onset. It should also be pointed out that motor electrodiagnostic testing findings are more often abnormal than sensory nerve results in early GBS. Blink reflex studies are often abnormal when there is facial nerve involvement.[26] Phrenic nerve conduction studies can be used to predict respiratory failure and the need for ventilation.[28] Reduced CMAP amplitudes of 0%–20% of the lower limit of normal carry a poor prognosis.[29]

The diagnostic yield of various neurophysiological criteria may vary in different subforms of Guillain–Barré syndrome, whose prevalence varies in different geographical areas. In a recent study the diagnostic sensitivity of Albers et al,[30] Cornblath,[31] Ho et al,[32] Dutch GBS Study Group,[33] Italian GBS Study Group,[and Albers and Kelly criteria[35] were evaluated and correlated with clinical subtypes of GBS, duration, severity, and outcome.[36] The sensitivity of nerve conduction study in the diagnosis of GBS and in different clinical subtypes of GBS was highest using Albers criteria (88.2%) and lowest using Cornblath criteria (39.2%). As per Ho et al, patients could be categorized into AIDP (86.3%), AMAN (7.8%), and AMSAN (5.9%).

Electrodiagnostic fi ndings in Guillain–Barré syndrome

Incidence of antiganglioside antibodies in GBS has varied widely in different published series.[37,38] Its much more common in AMAN variant than AIDP. The incidence was found to be 58% in a study of 60 patients of GBS by Meena et al (Unpublished data from NIMS, Hyderabad). Although antiganglioside antibodies have been implicated in the pathogenesis of GBS, assaying antiganglioside values in a patient with GBS other than MFS at the present time has no diagnostic value in routine practice.

Variants of Guillain–Barré syndrome

Commonly recognized variants include those with axonal forms, variants based on particular fiber-type involvement (sensory or autonomic), and MFS. Variants with regional or a markedly asymmetric distribution also occur.[1] There are also differences in abruptness of onset and time to reach nadir, which can complicate diagnosis and decisions about treatment. For example, some patients have clinical features and disease course similar to GBS except for a slower progression (ie, progression that lasts longer than 4 weeks); this disease is sometimes referred to as subacute inflammatory demyelinating polyradiculoneuropathy (SIDP);[39,40] however, in many respects SIDP is like GBS and often should be treated as such. AMSAN and AMAN are two variants characterized by immune attack directed at axons rather than Schwann cells and myelin.

AMAN occurs in large epidemics during summer in northern China and more sporadically elsewhere.It mostly affects children and young people, usually from rural areas. Onset of motor weakness is abrupt. In addition to acute pure motor paralysis, many patients have transient neck and back stiffness early in the course with resolution within day. Recovery usually begins within 3 weeks and is often complete and may take longer. Mortality rate is roughly 3%–5%. Sensory nerve conduction studies are normal and motor nerve studies are remarkable for low or absent CMAP amplitudes with normal conduction velocities. Denervating potentials are seen on needle electromyography.

AMSAN shares many pathological features with acute motor axonal neuropathy but differs clinically from it in patient age of onset (usually adults rather than children), geographic distribution (can occur anywhere), time of onset (not only summertime), involvement of sensory nerves, course (protracted), and outcome (usually severe residual disability). It has an abrupt onset and rapid progression with most patients requiring mechanical ventilation within a few days of symptom onset. Motor nerves are electrically inexcitable early in the disorder. Sensory nerve conduction studies are also abnormal. Widespread denervation is seen on needle examination. The course is protracted and outcome poor, with only 20% ambulating at 1 year.

MFS: The more recognizable and distinct regional variant of GBS is MFS.Like GBS, the onset of MFS often follows an infection, for example C. jejuni.MFS patients classically present with external ophthalmoparesis, areflexia, and ataxia,although MFS patients often present with fewer components of the classical clinical triad or with additional clinical features (facial weakness, oropharyngeal weakness, internal ophthalmoparesis, central nervous system involvement). Bickerstaffs brainstem encephalitis (BBE) is a related syndrome in which alteration of consciousness or conticospinal tract signs are seen in addition to ophthalmoparesis and ataxia. Many patients with MFS or BBE also have “overlapping GBS” with flaccid quadriparesis.Anti-GQ1b antibodies are present in 95% of patients with acute MFS[51] and in approximately two-thirds of patients with BBE. The recognition of various clinical presentations and the high sensitivity and specificity of anti-GQ1b antibody testing suggest rubric name of “anti-GQ1b antibody syndrome.”

Anti-GT1a antibody without anti-GQ1b reactivity is found in patients presenting with the pharyngeal–cervical–brachial (PCB) variant of GBS.More than half of MFS patients will have cytoalbuminological dissociation on CSF analysis performed within the first 3 weeks of disease onset. In MFS, motor nerve conduction studies in the limbs are usually normal or only mildly abnormal with slight reductions in compound muscle action potential amplitudes and conduction velocities.Conduction block and temporal dispersion are not a feature of MFS. Sensory nerve action potential amplitudes are usually moderately to severely reduced, more so in the upper extremity sensory nerves (eg, median) than the sural nerve. Blink reflex R1 delayed or absent. MRI of the brain frequently demonstrates cranial nerve enhancement (eg, occulomotor nerves) in MFS and high-intensity abnormalities in the posterior fossa, white matter, or thalami in patients with BBE.MFS is generally a benign, self-limiting conduction. Almost all treated and untreated patients return to normal activities within 6 months of disease onset, usually with resolution of ophthalmoplegia within 1–2 months and ataxia within 3–4 months.

Other regional variants of

GBS are those that affect other specific areas of the body, such as only the face or the afferent sensory and autonomic systems.

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