Guillan-Barre Syndrome: A personal view
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In the fall of 2007, the author’s mother was stricken with a mysterious malady that left her unable to stand or walk. After a short period she was diagnosed with Guillain-Barré syndrome. Treatment for this led to a further diagnosis of a serious urinary tract infection, and still further to an ultimate diagnosis of cancer of the bladder. In this paper, the author intends to discuss this still-puzzling syndrome, its possible relationship to cancer, its proven relationship to serious infections, its most common treatments, and its morbidity and mortality rates.
What Is GBS?
Guillain-Barré syndrome (GBS) is, according to Newswanger and Warren (2004), “an eponym for a heterogeneous group of immune-mediated peripheral neuropathies” (p. 2405). The syndrome was named in 1916 for its discoverers, Georges Guillain and Jean Alexandre Barré (Olshanky, 2007), although “the French physician Jean Landry had described the condition in 1859” (p. 1). The effect on the body is startlingly similar to that of multiple sclerosis, in that GBS destroys the myelin sheath. Each of the conditions in this grouping has one commonality: They are all set off by preceding infections. In the case of the author’s mother (hereafter referred to as “L”), the trigger was apparently a severe infection of the urinary tract (UTI). The author has yet to find any published information citing UTIs as being connected to GBS in any way.
Most commonly, according to Olshansky (2007), preceding infections are of the acute respiratory or gastrointestinal types (p. 1). His statement is supported by data from Samuels (cited in Olshansky): “Recent infection with Campylobacter jejuni, cytomegalovirus (CMV), Epstein-Barr virus and Mycoplasma pneumonia have been serologically implicated in 32 percent, 13, percent, 10 percent, and 5 percent of patients with GBS, respectively”(p. 1). Other possible precedents, according to Mantay, Armeau, and Parish (2007), include “vaccinations against influenza, meningitis, and tetanus toxoid” (p. 1). It is important to note that while these are recognized triggers, they are not shown to directly cause GBS. No research has yet explained satisfactorily why some people contract GBS and others do not. Mantay et al. state that while correlations are clear from the various studies that have been completed, “a direct causation has not been proven” (p. 1).
How Is GBS Diagnosed?
Mantay, Armeau, and Parish (2007) state that diagnosing GBS “is usually not difficult for the neurologist, but can be challenging for the doctor of first contact who may not have seen a case since medical school” (p. 7). This held true for L. The author’s personal opinion is that the mystery was exacerbated by the hospital being a small-town/rural facility; the nearest city of size is approximately an hour away, and Chicago is roughly two hours’ drive. Given the rarity of GBS, which strikes only 1-3 persons in 100,000 annually in Europe, Australia, and the United States (Newswanger and Warren, 2004, p. 2405; Mantay et al., p. 1), it was of little surprise to the author that several days passed before the diagnosis was confirmed. Newswanger and Warren also note that usually, a “definitive diagnosis” is impossible until at least five days after the symptoms first appear (p. 2406).
Signs, Symptoms, and Subtypes
According to Newswanger and Warren (2004), GBS sufferers “typically present with weakness accompanied by tingling dysesthesias in the extremeties” (p. 2405). Weakness is most pronounced in the legs, but arms can also be affected. Nerves in the head may be involved; this could result in the patient having the appearance of a stroke victim, or having difficulty speaking or swallowing. Pain is often a complaint, occurring in about 50 percent of patients (p. 2405).
There are five subtypes of GBS (Newswanger and Warren, 2004). In L’s case, no further delineation was given to the immediate family aside from the initial diagnosis. Such information would be in the patient’s medical record, to be sure, but the author cannot verify her educated assumption. The five variants are: acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor sensory axonal neuropathy (AMSAN), Miller Fisher syndrome, and acute panautonomic neuropathy (p. 2407). Each subtype has its own set of signs and symptoms beyond the paralysis common to all.
A condition similar to GBS is CIDP, or chronic inflammatory demyelinating polyneuropathy. The main difference in presentation is the rapidity of the onset. CIDP usually presents as a weakness in the legs that develops over a period of months (GBS-CIDP Foundation International, “About CIDP,” How Is CIDP Diagnosed?). Treatment is very similar, using IVIg or plasmapheresis (see below, “Treatment, Not Cure”), but steroids have been shown to be useful as well (How is CIDP Treated?); they are not indicated for use in treating GBS.
AIDP: Most Common
Olshanky (2007) explains that “. . . (AIDP) is the most common subtype of GBS in the U.S.” (p. 1). Hindsight suggests to the author that this was likely the variant that struck L. He further describes “rapidly progressing weakness, numbness, and tingling in the lower extremities” (p. 1). L was a very active woman in her late 70’s, who spent hours outdoors in the spring and summer tending to her gardens. On the day she was transported to the hospital, she had fallen a total of four times within a matter of hours when her right leg refused to support her weight. Three times, her husband was able to help her to stand, and she resumed activities. The incidents grew closer together as the day progressed, until in the late afternoon she fell while stepping onto the back porch. In her position, she was unable to assist her husband in getting back onto her feet, and she told him to call the local ambulance service.
L’s primary care physician called the specialist in sports medicine who had only weeks before performed a very successful repair of L’s left rotator cuff. The specialist found nothing relating L’s inability to put weight on her right leg in any of the care he had provided to her. After this consult, the two doctors conferred again and determined that a neurologist needed to see L. This visit ruled out transient ischemic attack and resulted in a lumbar puncture. Olshansky (2007) explains: “The clinical diagnosis of GBS needs to be confirmed by cerebrospinal fluid analysis and nerve conduction studies. Lumbar puncture is indicated in every case of GBS” (pg. 2).
Treatment, Not Cure
Within a day of that visit, L received the diagnosis of GBS and was started on the most common treatment: “high-dose intravenous immunoglobulin (IVIg; 400 mg per kg daily for five days)” (Newswanger and Warren, 2004, p. 2408). One reason IVIg is preferred is the ease of delivery. It also results in “fewer complications” and is “more comfortable for the patient” (p. 2409). Complex biochemical reactions brought about by IVIg treatment have the effect of “(m)odulation of the immune system . . . through multiple mechanisms involving the constant and variable regions of immunoglobulin class G (IgG)” (p. 2409). There are also effects on “receptors on macrophages and B cells” as well as on a specific T cell (p. 2409). The author can attest to the comfort level of this treatment as witnessed during visits with L while it was being administered. She claimed it was no more uncomfortable than any IV she had had previously.
By the end of the fifth day of treatment, L was able to move her right leg, bending the knee; however, she remained unable to stand.
Plasmapheresis: An Alternative Treatment
It is not known precisely why plasmapheresis or “plasma exchange” is effective. The Mayo Clinic’s information page on treatments (Mayoclinic.com, Guillain-Barré syndrome, “Treatments and Drugs”) explains it in this way: “(S)cientists believe that plasmapheresis rids plasma of certain antibodies that contribute to the immune system attack on the peripheral nerves.” Since the plasma used in replacement does not contain the antibodies the patient’s body is creating, a series of plasmapheresis treatments seems to effectively remove those antibodies and allow remyelination.
While effective treatments exist for GBS, the fact remains that it is an incurable disease. Recovery rates are discussed in the next section, “Follow-Up Therapy.”
Following treatment by either plasmapheresis or IVIg, GBS patients usually move on to physical/occupational therapy. At the very least, they will need training in how to use a wheelchair properly in addition to exercises for strengthening the weakened muscles. Perhaps a walker will be indicated instead after a time; in L’s case, she was learning to use a walker within three months of the end of the IVIg treatment. Had the cancer not continued to weaken her, and had she not contracted a drug-resistant gastrointestinal infection, that course could well have continued for her. This seems to be well within the lines of normal and expected recovery. According to Newswanger and Warren (2004), “(a)pproximately 85 percent of patients with GBS achieve a full and functional recovery within six to 12 months” (p. 2409). Two factors that could have meant a poorer prognosis were L’s advanced age and the rapidity of onset. Newswanger and Warren, citing Fletcher, Lawn, Wolter, and Wijdicks, state “(factors that can mean a slower, less complete recovery) include age older than 60 years; severe, rapidly progressive disease; and low nerve conduction amplitudes on distal stimulation” (p. 2409).
In addition to the drugs and therapy prescribed by the physician, there could very well be a need for counseling by a mental health professional. The Mayo Clinic’s information page, “Coping and Support,” discusses the devastating effect GBS can have, especially if recovery takes longer than the patient expects. L’s immediate family was told at one point that she might have been coming home for the holiday season, if all went well. The cancer and the after-effects of its treatment made that impossible, however. She spent Christmas day with her daughter and granddaughter, in the dining room of the skilled nursing facility where she had moved after radiation therapy for the cancer was completed. One month prior to that, she had been walking 50 feet with a walker, three times a day. While she did not speak to a counselor with a medical or psychiatric/psychological background, L did have frequent regular discussions with her pastor regarding her condition and the likely outcome. These visits clearly helped her come to terms with her new reality.
Cancer and GBS
Initially the author intended to explore the relationship of GBS to cancer in various forms. The resources she has located indicate that very little correlation has been found. That is not to say, however, that the two diseases cannot or do not coexist. Halls, Bredkjaer, and Friis (1988) report that of 34 GBS patients in a Copenhagen, Denmark hospital, six were found to be suffering from some form of cancer. These patients’ GBS took a longer course than the non-cancer sufferers, and their evidence of improvement was much less (abstract).
Another study, this one from Italy by Vigliani, Magistrello, Polo, Mutani, Chio, and the Piemonte and Valle d’Aosta Register for Guillain-Barré Syndrome (2004), shows an apparent relationship, at least in some cases. “In the nine-year period, 435 incident patients with GBS were found. Nine of them developed cancer in the six months preceding or following GBS; in seven of them, the diagnosis of cancer and GBS was concomitant. The expected number of malignant tumours was 3.7 (using the incidence in Piemonte) and 3.8 (using the incidence in Turin); therefore, the odds ratios were 2.43 (95 % CI, 1.11-4.62) and 2.37 (95% CI, 1.09-4.50), respectively (p<0.01)” (abstract).
In L’s case, the advanced state of the bladder cancer indicated that it had been present for quite some time prior to the onset of her GBS. The findings of the Turin study might have some correlation to the situation surrounding the comorbidity of L’s cancer and GBS; however, the family was not informed about how long the cancer had likely been present in L’s body at the time of GBS onset.
Mortality rates directly related to GBS are relatively low. Lawn and Wijdicks (1999) explain that, in one study, only 4% of patients with GBS died directly as a result of the disease. Of these, the most common cause of death was “ventilator-associated pulmonary infection, predominantly in elderly patients with significant comorbidity” (abstract). Hahn, cited in Newswanger and Warren (2004), claims the “mortality rate is less than 5 percent in tertiary care centers with a team of medical professionals who are familiar with GBS management” (p. 2409).
The Turin study (Vigliani et al., 2004) goes on to say “the mortality in GBS patients with cancer was higher and was the final cause of death in two patients affected by severe cancer. These results suggest a possible correlation between some cases of GBS and cancer” (abstract). The abstract is not inclusive of discussion regarding this correlation. The author is given to suspect that GBS as the ultimate cause of death was very likely related to intubation required by an advanced stage of that disease, since the research for this paper clearly points to that being the most common result. L had no need for intubation since her GBS was caught at the earliest possible point in the disease course, and she responded well to the IVIg treatment.
L’s primary care physician and the neurologist who ultimately diagnosed her GBS both discussed the issue of mortality with her before the diagnosis of bladder cancer was made, in terms of having caught her GBS very early in its course. In some cases the disease “advance(s) so rapidly that . . . intubation . . . and ventilation may be necessary within 24 hours” (Newswanger and Warren, 2004, p. 2408). As stated earlier, ventilation-related infections are the major cause of death related to GBS. L was one of the lucky ones who required no such intervention.
The initial intent of the author’s study was to define GBS and its variants, to explore current treatments, to investigate connections between GBS and cancer, to discuss rates of morbidity and mortality, and to come to a better understanding of her mother’s experience with the disease through research.
During the course of writing this paper, the author did indeed garner more insight into what happened to her mother during the last six months of her life, with regards to the GBS that led to her ultimate diagnosis of bladder cancer. The two diseases can exist side by side, but no real correlation has been proven; such is only suggested by some of the research available. No research the author could locate references UTIs as possible triggers of GBS, but that was clearly the case with L. The rarity of GBS is underscored in nearly every reference available, making clear the difficulty in diagnosing the disease at the primary care level. L was given the most common treatment, IVIg infusion. Her follow-up care was normal for GBS patients, and included physical and occupational therapies from doing leg lifts to learning to use a walker. Had there not been complications from her cancer—both the disease itself and the treatment she chose—she likely would have been among the 85 percent who recover nearly full mobility, according to her doctor. Despite her advanced age (defined as “over 60”), her mental state contributed positively to the amount of recovery she achieved before her death—and to the manner in which she greeted death when it came.