Case 5: Guillain-Barré
Syndrome
A
14-year-old boy awoke one morning 2 weeks after an episode of influenza with a
mild weakness in his legs; his skeptical parents wondered if this was a ploy to
avoid school but during the day he developed pain in his back and 'pins and
needles' in his feet. He was considerably worse the next day and complained of
weakness in his arms as well, and by the evening he was unable to stand and was
admitted to the hospital with suspected acute idiopathic inflammatory
polyneuropathy. Lumbar puncture showed no cells but a slightly raised protein level
in the CSF. Peripheral nerve conduction studies the next day revealed
demyelination There was concern when he developed autonomic dysfunction, with
bladder atony and ileus that evening, and he was treated with high-dose
intravenous immunoglobulin (1g/kg body weight for each of 2 days); he made a
complete recovery in 14 days. Antibodies
to ganglioside GD1 were subsequently shown in the pretreatment serum simple.
Summary
Guillain-Barre Syndrome is caused by an autoimmune disease that destroys
the myelin sheath of nerves in the peripheral nervous system. The initial phase
of the disorder is often characterized by an infection of Campylobacter jejuni
or an episode of influenza. After the occurrence of the infection, T-cell and
antibodies in the mucosa of the gastrointestinal system can now recognize
self-antigen resulting in molecular mimicry (antigenic similarity between two
different molecules. After the pathogen
has been eradicated from the host, memory B cells remain in the circulation. Sometimes,
anti-jejuni immunoglobulins will recognize ganglioside epitopes
similar to those of the pathogen, but found in the host cells. This disorder can be accompanied by
complications such as general respiratory muscle weakness (e.g. diaphragm, internal/external
oblique and accessory muscles).
The response mediated by these antibodies is considered Type II
hypersensitivity. Type II hypersensitivities are characterized by the
generation of plasma cells that can produce IgG. After the cross-reaction,
immune complexes and danger signals are produced that recruit part of the
immune response. The most affected component in this reaction is the myelin
sheath of the nerves. This causes a loss
of sensation accompanied by weakness and areflexia. Hypotension and arrhythmias
have been reported. Also a decrease of
loss of electrical conduction is also observed and can be evaluated by the 2
point discrimination test. Sensation is
first affected in the lower limbs with pins and needles of the upper limbs.
There are elevated levels of proteins in the cerebral spinal fluid because of
vasodilation via cytokine activity.
Full recovery is only seen in 80% of patients. Those who do not recover experience unusual
levels of fatigue and muscle weakness/pain. In order to recover, patients
undergo the removal of harmful molecules by plasmapheresis. In this process,
blood is drawn from the body and centrifuged followed by return of red blood
cells to the subject. Other types of treatment involves the administration if
immunoglobulins with the capacity to ameliorate the immune reaction’s strength.
Glucocorticoids have been attempted for treatment without substantial success. Physical
therapy has proven to be beneficial at improving the capacity to regain muscle
strength endurance and movement.
Questions
1-What are the main alterations observed in the case?
Demyelination of
peripheral nerves. After infection with Campylobacter
(most commonly, but can also be due to CMV, vaccination, etc) the immune system
attacks ‘self’ due to molecular mimicry.
2-How can be explained the symptoms and signs presented by
the patient?
Ascending
paralysis. Weakness begins in the feet and goes up to trunk and arms (i.e.
lower motor neuron, peripheral neuropathy).
3- What components of the neurological system are affected
in this case?
Schwann
cells that produce the myelin of peripheral nerves are targeted by
auto-antibodies- demyelination occurs.
4-What is expected of the evolution in these types of patients?
-
Sensations of ‘pins and needles’ (i.e. paresthesias) that begin
in the lower extremities and ascend to the trunk and upper extremities.
-
The sensation of numbness becomes more intense as the symptoms
radiate.
-
Patient is unable to walk or perform any bodily movements.
- As the neuropathy
progresses, patient has difficulty breathing and needs to be placed on a
ventilator.
If damage is restricted
to the myelin only, then the patient is expected to fully recover after a few
weeks to months. If damage
to axons occurs, recovery is contingent on the regeneration of the nervous tissue.
References
Hardy
TA, Blum S, Mccombe PA, Reddel SW. Guillain-barré syndrome: modern theories of
etiology. Curr Allergy Asthma Rep. 2011;11(3):197-204.
Luc
Jasmin MD, PhD.Guillain-Barre Syndrome. National Institute of Health. 2012
Available at: http://www.nlm.nih.gov/medlineplus/guillainbarresyndrome.html Accessed
May 8, 2013.
NINDS
Guillain-Barré Syndrome Information Page. National Institute of Neurological
Disorders and Stokes. 2011. Available at: http://www.ninds.nih.gov/disorders/gbs/gbs.htm Accessed
May 8, 2013
Nyati
KK, Prasad KN, Rizwan A, Verma A, Paliwal VK. TH1 and TH2 Response to
Campylobacter jejuni Antigen in Guillain-Barré Syndrome. Arch
Neurol.2011;68(4):445-452. doi:10.1001/archneurol.2011.51.
P.A.
van Doorn, MD, A. Brand, MD, et al. High‐dose intravenous immunoglobulin treatment in chronic
inflammatory demyelinating polyneuropathy. Neurology February
1990 vol. 40 no. 2 209. doi: 10.1212/WNL.40.2.209
Peripheral
Neuropathy. 2012 Available at: http://www.merckmanuals.com/professional/neurologic_disorders/peripheral_nervous_system_and_motor_unit_disorders/peripheral_neuropathy.html?qt=&sc=&alt=. Accessed
May 7, 2013.
It is interesting to see how cells with the same function but different in their histology component produced two different pathologies. For Guillain-Barre and Multiple Sclerosis, both destroyed the myelination of the nerves. Guillian-Barre can be distinguished because it is a peripheral nervous system defect, which would affect only the Shwann Cells. In Multiple Sclerosis, the affected cells would be the oligodendrocytes. Also as Shawn Cells myelinates only one axon of the PNS, as compared to the oligodendrocyte which myelinate multiples axons of the CNS, patients suffering with Guillian-Barre could have a better prognosis than patients suffering from Multiple Sclerosis.
ResponderBorrarGreat point in the above comment, about how the Schwann cells only myelenate one axon. And so Guillian-Barre can be better controlled than Multiple Sclerosis, which because its affect is on the central nervous system is more detrimental.
ResponderBorrarThe statement that really caught my attention was in the last question, I had no idea that damage could be done to the actual "axon" too! THAT sounds detrimental!
Guillian Barré syndrome may present as a type IV hypersensitivity reaction also called cellular hypersensitivity. In type IV hypersensitivity the antigen will activate the CD4+T cells leading to the release of INF- gamma and interleukin-2. Interferon gamma will over activated macrophages and IL-2 will induce maturation of T-cells into CD8- cytotoxic cells and both of these types of cells will be directed against the antigen. As described in this case the causing agent in Guillian Barré hypersensitivity reaction comes from Campylobacter jejuni. After a C. jejuni infection, the immune system is “sensitize” to its antigen, which is very similar to components from ganglioside and peripheral myelin, this is called molecular mimicry. After an exposure to these components from self-tissue (gangliosides, peripheral myelin), the immune system will be activated against these tissues and produce a cellular response mediated by macrophages and cytotoxic cells, causing the classic symptoms of ascending paralysis seen in this disease.
ResponderBorrarhttp://emedicine.medscape.com/article/136118-overview#a0104http://link.springer.com/article/10.1007%2FBF03160190
I found this topic interesting and looked for more information. Guillain-Barre´ syndrome (GBS) is often considered to be synonymous with acute inflammatory demyelinating polyradiculoneuropathy. But GBS has grown to include axonal variants and more restricted variants such as Miller Fisher syndrome (MFS). The reported incidence rates for GBS are 1 to 2 per 100,000 populations. In this case, it was mentioned Campylobacter jejunicytomegalovirus (CMV) and Epstein-Barr virus but we can see many other antecedent infections/treatments/procedures that have been identified with GBS, some examples are: Mycoplasma pneumonia, surgery, immunization, parturition and influenza virus.
ResponderBorrarElectrodiagnostic testing is performed to support the clinical impression that the acute motor paralysis is caused by a peripheral neuropathy. Electrodiagnostic testing of GBS patients often also demonstrates features of demyelination, such as temporal dispersion, significantly slow conduction velocities, and prolonged distal and F-wave latencies. This test is important because other conditions can be confused with GBS. Perhaps acute-onset myelopathy is the most commonly mimics GBS. Acute myelopathy may be caused: by transverse myelitis, acute spinal cord compression or spinal cord infarct. Symptoms include hyperreflexia, extensor plantar responses and trauma. For this condition, normal electrodiagnostic testing is obtained.
https://www.orpha.net/data/patho/Pro/en/GuillainBarre-FRenPro834v01.pdf
Trabajando en Guatemala como interprete medico, vi varios casos de paralisis muscular en ninos. Me impacto bastante porque soy ninos sin ningun trauma que parecen saludables pero comienzan a experimentar debilidad y despues no pueden caminar sino con mucho esfuerzo. Estos ninos son condenados a cama durante periodos de debilidad extendida. Ojala en el futuro se puedan desarrolar tratamientos mas economicos para ayudar a estos ninos en paises en desarrollo.
ResponderBorrarVisto la teoria que estas enfermedades representan las sequelaes a infecciones bactereogenicas, me tiene sentido que uno encontraria mas casos de debilidades musculares progresivas y autoimunes en Guatemala. Esto seria porque los sistemas de saneamiento son menos desarrollados en Guatemala que en paises mas desarrollados. Me pregunto cual seria la epidemiologia de estas enfermedades en paises en desarrollo vs. el mundo industrialisado. Vi varios casos en Guatemala, pero desconozco la prevalencia en otros paises. Si se fuese a estudiar la epidemilogia, o si ha ya sido estudiado, representaria una fuente posible de apoyo a esta teoria de sequelaes a infecciones bacteriogenicas.
By Charlie V Moreno
ResponderBorrarType IV hypersensitivity? Type II? Confusion has spread throughout the class about which type of hypersensitivity is displayed with GBS. In one hand we have our professor telling us that it's type II, while our most trusted and top rated book for preparation of the boards tells us that it is type IV. I think the confusion is due to the nature of the disorder. While it is true that GBS involves antibodies, its pathology is actually more related Th1 lymphocytes. Please tell me what you guys think and also provide the source that helped you arrive at your conclusion.
El caso de Guillain-Barré Syndrome es uno de los casos que mas me intrigó. Me parece interesante como la demielinización ocurre primeramente en las piernas y no en los brazos. También es interesante el transcurso de esta condición. Es triste pero asombroso ver como una infección de Campylobacter jejuni resulta en una inflamación aguda desenlazándose en una neuropatía periferial. El mismo hecho de ver que una reacción inmune al epítope del Schawn cell por medios de “molecular mimicry” son cosas que ni sabía que podían ocurrir. Si tengo que añadir que aunque arriba menciona que GBS se trata de una hipersensitividad tipo II, he encontrado en diversas fuentes que al igual que esclerosis múltiple, GBS es una hipersensitividad tipo IV.
ResponderBorrarI think this syndrome is pretty interesting and important to understand because of it's similarities with Myasthenia Gravis. However, they're brought on by two completely different reasons. Guillain-Barre being characterized by an initial episode of influenza. Whereas MG is due to a type 2 hypersensitivity reaction to acetycholine receptors at the synaptic clefts of neuromuscular junctions. Also, to learn how important it is to catch and treat Guillain-Barre as soon as possible due to the ability to make a full recovery if only the myelin sheaths are affected opposed to having the axons affected at which point recovery would depend on nervous tissue regeneration.
ResponderBorrarComo bien se explica en la información presentada, el infectarse con Campylobacter jejuni puede resultar en complicaciones como lo es Guillian Barre Syndrome. Con respecto a este tema se han estado realizando estudios con diferentes plantas (Acacia farnesiana, Artemisia ludoviciana, Opuntia ficus-indica, y Cynara scolymus) cuyos productos naturales parecen ser una terapia potencial para controlar la contaminación con este microorganismo.
ResponderBorrarThere is a controversy in literature, if GBS is type II or type IV hypersensitivity. The pathophysiology of GBS is a combination of both. The initial phase where antibodies antigagliosides are produced is classified as type II hypersensitivity. However if we are going to classified the disease by the mechanism o damage to the nerve it is classified as type IV. I have a reference at my office that I will try to share tomorrow to clarify this controversy among the students. But this is an example that no thruth is absolut. Science is a dynamic universe and what it was the thruth in the past can change. The same happenned to the controversy with arthritis rheumatoid and if it was type III or IV. I will share the paper tomorrow to the class.
ResponderBorrarGood post....thanks for sharing..
ResponderBorrarTOSHIBA PVM-375AT