Guillain Barre Syndrome (GBS)

GBS is a syndrome; i.e., a collection of symptoms and signs that have different causes and different pathologies.  The common factors linking the different forms of GBS are that is is an autoimmune disease that affects the peripheral nervous system (the nerves in the head, body and limbs but outside the brain and spinal cord) and that it evolves rapidly, over a few weeks.  The commonest form of GBS is also known as acute inflammatory demyelinating polyneuropathy (AIDP) because the immune attack damages the myelin sheath that insulates the nerve fibres (axons).  “Polyneuropathy” just means many nerves and essentially is synonymous with the more commonly used “neuropathy”.  Another common form of GBS is acute motor axonal neuropathy (AMAN) that looks identical at the bedside but the immune attack is directed against the axons.  Some forms of GBS are restricted in their distribution, affecting only a few nerves.  The best known of these is called the Miller Fisher syndrome (MFS) in which the immune attack primarily affects the nerves controlling the eye muscles.

GBS is a treatable disease and the outcome is usually good even for those with severe weakness.  About 70% of patients recover full strength while some are left with variable degrees of weakness, mainly in the form of foot drop and hand weakness. 50%-80% will have residual fatigue or poor stamina which can last for years, even though their muscle strength returns to normal, and others will have residual pain.  Patients rarely die of GBS and those that do are nearly always older (over 75) or have other medical problems. The most important treatment is general medical support to prevent complications.  Specific treatment of GBS speeds recovery, however it does not impact on the final degree of recovery.

GBS is an autoimmune disease.  Our immune system normally protects us against disease by killing harmful invading pathogens, but with GBS, this normally protective response is hijacked and instead attacks our own nerves.  What causes this to happen is not precisely known but about 70% of cases follow an identifiable event, usually an infection.  In NZ, the commonest identified infection is caused by an organism called Campylobacter jejuni, a common cause of food poisoning.  NZ has one of the highest rates of C. jejuni infection in the world and due to this GBS incidence is almost double that of other western countries.

GBS is an acute paralytic disease; that is, there is rapidly evolving weakness.  By definition, GBS can progress for up to 4 weeks but about 80% of cases stop progressing within 2 weeks.  If a GBS-like disease progresses for longer it is defined as CIDP – chronic inflammatory demyelinating polyneuropathy – which is discussed elsewhere.  The weakness can affect any muscle that is under voluntary control including face, speech and swallowing, breathing and limb muscles.  In rare, very severe cases paralysis can be almost complete with only blinking and some eye movement preserved.  The diaphragm, the muscle that controls breathing, is affected in about 25% of cases and may necessitate mechanical artificial ventilation.  If swallowing is severely affected it may be necessary to maintain nourishment through tube feeding.  Occasional cases are restricted to a few muscles; e.g., 10%-15% of cases have the Miller Fisher variant in which weakness is restricted to the eye muscles, perhaps with mild facial weakness and difficulty with speech and swallowing.  Almost all cases of GBS have absent reflexes although that is not always so in the very earliest stage of the disease.  However, if reflexes are still present after 2-3 days the diagnosis should be reconsidered.  Absent reflexes have no effect on the patient but are a very important finding the doctors look for in making the diagnosis.

Despite this sometimes severe and always frightening weakness, prognosis is good.  After progression stops there is a variable period of clinical plateau where there is neither deterioration nor improvement and then recovery begins.  Recovery usually follows a steady trajectory but about 5% of cases experience a brief setback (relapse) which is usually mild and lasts no more than a day or two.  Mild cases may be back to normal within 2-3 months while those who are severely affected may take up to 3 years to recover.  About 70% recover full strength while about 25% are left with some weakness.  Even with the best medical care about 5% of patients die, usually the frail and elderly or those with other serious illnesses.

Sensation is minimally affected in GBS.  Patients may notice tingling feelings, particularly early as the weakness is just beginning, but overt loss of sensation is rare.  About 40% of patients have pain that may occur during the acute phase of the illness or develop as weakness is improving.  It is usually mild and improves spontaneously or with treatment.

The unconscious functions of the body such as heart beat, blood pressure, intestinal function and bladder function are also affected but usually to a very minor degree.  It is important to monitor carefully for these abnormalities since they may have serious consequences which, along with the evolving weakness of the diaphragm, which is why patients are usually managed in an intensive care unit.

GBS is an autoimmune disease.  The immune system evolved to recognise and eliminate foreign invaders like bacteria and viruses but it can be fooled into believing components of your own body are foreign and mounts an attack against itself.  Diseases such as rheumatoid arthritis, psoriasis and many others are autoimmune.  In the commonest form of GBS (acute inflammatory demyelinating polyneuropathy, AIDP) the attack is mounted against the myelin sheath that insulates the nerve while in the GBS variant, acute motor axonal neuropathy (AMAN), the attack is mounted against the axon, the cable that transmits electrical messages down to the muscle and up to the spinal cord and brain.  Why the immune response becomes hijacked is not entirely clear but a leading contender is “molecular mimicry”.  About 70% of GBS cases follow an infection and it is thought that a molecule on the infecting organism sufficiently resembles a molecule on the nerve that the immune system is tricked into thinking the nerve is foreign.  There is abundant evidence that this is the case for GBS that follows infection with Campylobacter jejuni, a common cause of gastroenteritis, but evidence is lacking for other infections.  Why the immune response is then turned off so that GBS recovers is unknown.  Since GBS is an autoimmune disease it therefore follows that specific treatments for GBS such as IVIg and therapeutic plasma exchange are treatments that target the misdirected immune response.

The diagnosis of GBS is primarily based on the clinical findings of rapidly evolving weakness and absent reflexes. The diagnosis is usually confirmed by performing a lumbar puncture (LP) and analysing the spinal fluid for increased protein levels and by nerve conduction studies (NCS). NCS are done by stimulating nerves with an electrical current and recording the responses from the muscles. The LP and NCS are unpleasant tests and many GBS patients recall them with a degree of dread. However, they are very important in distinguishing GBS from other causes of acute weakness.

GBS is a treatable disease. The most important treatment is general medical support to prevent complications. All patients should be admitted to hospital and closely monitored for breathing difficulties or abnormal heart beat and admission to an intensive care unit (ICU) may be necessary. In NZ not all hospital have adequate facilities to carry out such monitoring and patients in rural areas or small towns may need to be transported to a major hospital for their initial care. Treatment to prevent blood clots and bedsores due to immobility may be needed. Meticulous nursing care and physiotherapy are critical in the early stages of the disease. Emotional support and education for the patient and loved ones is also important as it is extremely frightening to experience loss of muscular control, including breathing function. A visit from a former patient who has made a good recovery can be very reassuring and in NZ a network of trained hospital visitors is available who can be accessed through the NZ Support Group Trust.

Specific treatment of GBS speeds recovery. In several major international studies treated patients spent less time in the ICU, less time in the acute care hospital and functioned better after one year than those who did not receive treatment. However, the final degree of recovery was no better. Treatment is most effective when started early so early diagnosis is important. Ideally treatment should begin within a few days of weakness onset. If delayed more than two weeks the treatments are probably not effective although it is usually still tried. Two treatments have been shown to be effective and they are equally effective, safe and tolerable. The most common treatment in most NZ centres is an intravenous infusion of blood product called immunoglobulin (IVIg) but some hospital prefer a procedure called therapeutic plasma exchange (TPE) or plasmapheresis, in which blood is withdrawn, the blood plasma is separated and discarded, and the red blood cells are returned along with donor albumen. TPE requires sophisticated equipment which is not available at all NZ hospitals which is why many doctors prefer IVIg. Each of these treatments is given over several days; 4-5 consecutive days for IVIg and 5 treatments on alternate days for TPE. Allergic reactions, low blood pressure and irregular heart beating can occur with each of these treatments so they should only be administered in a facility that can provide close monitoring.

Once the patient is stable and the appropriate treatment has been administered a period of rehabilitation is usually needed. This will start in the acute care hospital with increasing physiotherapy (PT), but most cases will benefit from an additional period of inpatient treatment in a rehabilitation hospital. It is always a goal to get the patient into their own home as quickly as possible but home-based PT and other forms of assistance with care will usually be needed. These are not always available outside the major cities so discharge to home may be delayed. Occupational therapy may also be recommended to provide assistive devices to optimise independence. Emotional support during the rehabilitation phase remains important to help the patient and loved ones deal with the frustrations associated with the recovery process.

The outcome is usually good even for those with severe weakness. About 70% of patients recover full strength while 25% are left with varying degrees of permanent weakness. A larger number 50%-80% suffer from long lasting residual fatigue or poor stamina even tough their muscle strength returns to normal. A few patients suffer long standing residual pain. Patients rarely die of GBS or its complications. Those that do are nearly always older (over 75) or have other medical problems. The rate of recovery varies and depends largely on the severity of the initial weakness. The mildest cases may leave the hospital within a few days and are back to their normal activities within a month or two while those with severe weakness may take a year or more to recover and are more likely to be the ones who recover incompletely.

Although the most famous medical account of the condition, leading to its current name, was not published until 1916 by French Neurologists Guillain, Barre and Strohl, it had been recognised more than 80 years previously. However, it was the 1916 observations and description that have become acknowledged as truly original. They were the first to recognise that the protein level in the spinal fluid was elevated but that there were no inflammatory cells, this distinguishing GBS from polio, the commonest acute paralytic disease of that era.  This remains one of the cardinal findings that helps establish the diagnosis of GBS.  Strohl was an electrophysiologist rather than a neurologist which may account for the loss of his name in the syndrome – or perhaps it was his lack of seniority and age – he was only 29 years old! Understanding of the symptoms of the syndrome has continued to evolve with the concepts of axonal degeneration and demyelination being recognised in the 1950’s together with the increasing use of nerve conduction testing and the impact of GBS in slowing down conduction velocity being first reported in 1956.

The greatest single advancement in the treatment of GBS came shortly after the Second World War with the development of artificial ventilation and this together with the introduction of intensive care units led to a dramatic fall in mortality rates in the 1950’s.

The understanding of GBS as an autoimmune process led to the development of immune therapies, particularly plasmapheresis in the 70’s and more recently high dos intravenous immunoglobulin. These became the first treatments available to reliably influence the course of the disease.

Jean-Alexandre Barré

Georges Guillain