Thursday, January 28, 2010
Friday, May 1, 2009
Thursday, April 30, 2009
* Acute idiopathic polyneuritis
* Postinfectious polyneuritis
* Landry’s paralysis
* Acute postinfectious polyneuropathy
* Acute polyradiculitis
Guillain-Barré Syndrome and the Autonomic Nervous System
Gareth J. Parry, M.D. Professor and Head
Department of Neurology University of Minnesota
The autonomic nervous system controls those functions of our bodies that we do not have to think about such as heart beat, blood pressure, sweating bowel and bladder function and sexual function. The weakness in GBS patients, including weakness of breathing muscles, so dominates the clinical picture that abnormalities of autonomic function often go unrecognized or is completely ignored. However, they significantly impact patient comfort during the early evolution of the illness. In addition, with the tremendous improvement in the care of ventilator dependent patients over recent years, abnormalities of cardiac autonomic function have come to constitute a major cause of death from GBS. Furthermore, these deaths are preventable with early recognition and appropriate treatment.
The most important form of autonomic instability in terms of survival is that which affects the heart and blood vessels. Tachycardia (rapid heart beat) is seen in many perhaps a majority of patients with GBS. By itself, this is not particularly important but as an indicator of early autonomic problems it is critical and is the principle reason why every GBS patient should have heart monitoring when first admitted to the hospital. About 20% of patients may have more serious cardiac arrhythmias. These do not always need treatment but are a reason for continued close cardiac monitoring. Some patients with serious irregularities of heart beat may require medication to stabilize the cardiac rhythm. In others, the heart beats too slowly and sometimes there are long pauses which may result in loss of consciousness. These latter patients may need a pacemaker to control the heart rhythm.
Hypotension (low blood pressure) is common in GBS and is usually made worse when the patient is upright (postural hypotension). Thus, patients may faint when they get up from bed. I have seen this problem many times, particularly in men who may have difficulty passing their urine when lying in bed. A kind-hearted nurse helps the patient to stand to urinate and the patient promptly gets very light-headed and may faint. In addition, involvement of the autonomic nerves to the bladder makes urination more difficult, compounding the problem. The same difficulties may be experienced during physical therapy. Other patients may develop severe hypertension. This may be sustained but is more often paroxysmal so that the patient may have periods of hypotension alternating with severe hypertension. Great care must be exercised in treating the elevated blood pressure because it is usually short lived. Medication may produce dramatic falls in blood leisure to dangerously low levels.
A number of factors may exacerbate autonomic instability. Mild hypoxia (lack of oxygen) may induce or exacerbate cardiac arrhythmias and this may be the first clue that a patient is developing respiratory failure. Succinylcholine, which is a drug frequently used to relax the muscles when patients are intubated in preparation for artificial ventilation, also induces cardiac arrythmias and should be avoided if possible in GBS patients. In addition, the act of intubation may cause arrythmias and every effort should be made to avoid emergency intubation by inexperienced personnel. By recognizing incipient respiratory failure before it becomes overt, these risks can be avoided or at least minimized. Plasmapheresis may also exacerbate autonomic instability. Both hypotension and cardiac arrhythmias may occur during the plasma ex-change and patients should continue on cardiac monitoring throughout the procedure. In patients who have objective evidence of autonomic instability I prefer to use intravenous immune globulin (IVIg), rather than plasmapheresis, to treat GBS patients.
Other autonomic problems that may occur include difficulty urinating which often necessitates catheterization, and constipation. Both are exacerbated by the inactivity resulting from the weakness. Abnormal sweating (drenching sweats) and flushing may also occur and may be mistaken for infection although fever is not present.
The severity of the autonomic instability is usually proportional to the severity of weakness but may still be seen in mildly involved patients. That is why I recommend cardiac monitoring for all patients for at least 24 hours or while the weakness continues to progress. The problems caused by autonomic instability are short lived and amenable to treatment so long term prognosis is excellent. However, constant vigilance during the acute phase of the disease is critical if an optimal course good outcome is to be achieved.
Macrophage and polymorphonuclear neutrophilic leukocytes (PMN) are essentially involved in the immune response of the body.
Motor deficit may begin proximally or distally in the extremities and sensory deficit is sometimes, but not always present.
Some cases have a dramatic and rapid deterioration, whereas others have a more subacute onset.
Dehydration and undernutrition may result.
An increase in WBCs may occur in many conditions including infection (viral, bacterial, fungal, and parasitic), allergy, leukemia, multiple sclerosis, hemorrhage, traumatic tap, encephalitis, and Guillain-Barré syndrome. The WBC differential helps to distinguish many of these causes. For example, viral infection is usually associated with an increase in lymphocytes, while bacterial and fungal infections are associated with an increase in polymorphonuclear leukocytes (neutrophils); marked CSF pleocytosis or the presence of polymorphonuclear granulocytes does not rule out the diagnosis of GBS.
Motor deficit may begin proximally or distally in the extremities and sensory deficit is sometimes, but not always present.
acutely high glucose causes alterations in osmolarity
Wednesday, April 29, 2009
Guillain-Barré Syndrome: The Untold Story
Guillain-Barré syndrome (GBS) is a rare neurological disorder that occurs when the body's immune system attacks the peripheral nerves in the body. This is known as an autoimmune disease and can be triggered following a surgical infection, or a stomach infection, or most any flu-like illness. In particular, infections of the gastrointestinal (GI) tract or respiratory system are most commonly associated with the condition. As the immune system fights off the infection, it mistakenly attacks the peripheral nerves.
Many cases are linked with recent bacterial or viral infections, vaccinations or surgeries, and trauma associated with inappropriate or deleterious therapies. Untreated conditions are also high on the order of possible causes. Case reports exist citing numerous medications and procedures as possible triggers. Many of the reported cases which seem to be triggered by a microbial infection may actually follow its course with a causal link to the drugs and/or the treatment, resulting in drug-induced decreases in the body's ability to recognise and attack invaders.
Since the widespread application of the vaccine preventing paralytic poliomyelitis, the number one cause of acute neuromuscular weakness in the developed world is Guillain-Barre Syndrome (GBS).
GBS has become an umbrella term for different polio-like disorders, representing a collection of clinical syndromes, some of which tend to overlap. GBS is the most common cause of acute flaccid paralysis, and is considered polio's closest mimic.
Guillain-Barre syndrome (GBS) is an inflammatory disorder of the peripheral nerves. The peripheral nerves convey sensory information (e.g., pain, temperature) from the body to the brain and motor (i.e., movement) signals from the brain to the body.
Guillain-Barre syndrome is not hereditary or contagious. It is an autoimmune disorder. It is an immune-mediated demyelination of peripheral nerves, usually seen 2-4 weeks after a viral illness, but also triggered after or during the course of treatment for a variety of other infective processes. Demyelination is the term used for a loss of myelin, a substance in the white matter that insulates nerve endings.
Also known as acute post-infectious polyradiculoneuropathy, GBS is the most common form of acute neuropathy. The disease affects peripheral nerves, nerve roots, and cranial nerves, particularly those innervating tongue, muscles of deglutination and extraocular muscles. Weakness of tongue and retropharyngeal muscles causes positional airway obstruction. Evaluation of the peripheral nerves reveals sections of the nerve with demyelination. Under microscopic exam, the nerve tissue is infiltrated with certain types of white blood cells, ie., lymphocytes.
The term "autoimmune disease" refers to a varied group of more than 80 serious, chronic illnesses that involve almost every human organ system. It includes diseases of the nervous, gastrointestinal, and endocrine systems as well as skin and other connective tissues, eyes blood, and blood vessel. In all of these diseases, the underlying problem is similar--the body's immune system becomes misdirected, attacking the very organs it was designed to protect.
Guillain-Barré syndrome is a 'post-infectious immune-mediated' disease. The hypothalamus (the part of the brain that works directly with the pituitary gland to produce hormones) is a "target" for 'post-infectious immune-mediated' disease.
Autoimmune diseases run the gamut from mild to disabling and potentially life threatening. Nearly all affect women at far greater rates than men.
Autoimmune diseases tend to occur together. Some examples of autoimmune diseases include lupus, Type 1 diabetes, multiple sclerosis, and Guillain-Barré syndrome. Because you have one autoimmune disease you may have a problem with your immune system, making you more susceptible to other autoimmune diseases.
These disorders may have many causes, but are probably the result of misdiagnosis and subsequent use of inappropriate and deleterious therapies. GBS can also be triggered by simple medications for something as common and inescapable as a cold virus. Another is that a particular medication, substance or combination may be the real cause of these disorders, but are often misdiagnosed or overlooked as a cause.
GBS is caused by an immune system response to a trigger, such as 'drug-drug' interaction, with possible additive effects when used in combination or concurrently as part of a drug regimen. It occurs when the immune system accidentally attacks the nerves in the lower back, stripping them of their protective myelin sheath. This causes these long nerves to 'short circuit' and cause changes in the sensation and function of the body. Paralysis results because nerve signals can't pass to muscles.
Guillain-Barré syndrome is a reversible condition that affects nerve signals in the body. As such, GBS can impact the hypothalamus which regulates homeostasis affecting regulatory areas for thirst, hunger, body temperature, water balance, and blood pressure and links the nervous system to the endocrine system.
GBS is primarily a disorder of nerve inflammation involving progressive muscle weakness or paralysis. It occurs more freequently in patients with meningitis, encephalitis, pneumonia, septicemia, severe malaria, bronchiolitis, and RSV infection, but many other disorders have also been implicated.
Guillain-Barré Syndrome may also include purely motor or sensory forms, chronic or relapsing disease, or a syndrome of ophthalmoplegia, ataxia and areflexia, known as the Miller Fisher syndrome (Hughes, 1995, p. 175). Most cases of GBS are caused by acute inflammatory demyelinating polyradiculoneuropathy (AIDP), but some are caused by acute motor axonal neuropathy (AMAN), or acute motor and sensory axonal neuropathy (AMSAN). The nerve or nerves may be inflamed, pinched, or 'lack blood flow'.
Miller Fisher Syndrome and Guillain-Barré syndrome are variant forms of acquired demyelinating polyradiculoneuropathy. Demyelinating neuropathies are commonly inflammatory and treatable. The concept of a systemic inflamatory response syndrome expresses the notion that the body responds in certain ways to a variety of insults, clinical and otherwise.
Clinical Presentation and Diagnosis of Guillain-Barré Syndrome
Guillain-Barré Syndrome is a frightening and disabling disease which strikes suddenly, sometimes with devastating effect. The diagnosis is based on a clinical examination of the symptoms and their distribution and is dependent on the typical clinical findings, such as areflexia, absence of fever, a rapidly evolving flaccid paralysis, and a likely inciting event.
The most characteristic epidemiological feature of Guillain-Barré Syndrome is the occurrence of an infection and subsequent treatment prior to the onset of illness.
GBS is an uncommon paralysing illness, caused by autoimmune inflammation of nerves, which most often follows a therapeutic regimen for a "flu-like illness". The disorder often manifests itself by a rapid onset of weakness and/or paralysis of the legs, arms, face and breathing muscles. Breathing is affected by weakening the muscles of the chest wall and diaphragm; in these cases, mechanical ventilation is required immediately.
Healthcare providers are encouraged to consider West Nile Virus in the differential diagnosis of prolonged flu-like illness, aseptic meningitis, encephalitis or atypical Guillian-Barre syndrome.
The original name, 'Landry's ascending paralysis', was for good reason. The arms and legs can progressively fail to work and the weakness can spread into the chest. GBS is the commonest peripheral neuropathy causing respiratory failure.
GBS is a prodromal malaise. In medicine, a prodrome is an early symptom indicating the development of a disorder or disease, or that an attack is imminent. For example low-grade fever, ill feeling, anorexia (lack of desire to eat), and chills, are all part of the prodrome for the Guillain-Barré syndrome. The prodrome may follow 12 to 24 hours of low-grade fever, a generally ill feeling, and abdominal or respiratory symptoms, but the beginning of symptoms is usually abrupt, marked by loss of appetite, dizziness, vomiting, and constipation (due to nerve damage to the bowel). Respiratory dysfunction may be compromised before signs are clinically obvious.
Dizziness, drowsiness, lethargy, ataxia, slurred speech, syncope, GI: constipation, nausea, vomiting, incontinence, and urinary retention have all been cited with adverse events.
GBS is a rare manifestation of serum sickness with a delayed hypersensitivity reaction, triggered by catastrophic over-stimmulation of the immune system. It is an immune-mediated type of delayed allergic response secondary to certain medications, or an iatrogenic immune mediated neuropathic reaction to contraindicated medications, or both. Deleterious effects of a therapeutic or diagnostic regimen causes pathology independent of the condition for which the regimen is advised. Notably, certain combinations of medications, such as penicillin and sulfa-based antibiotics can cause the body's immune system to react by overstimulation, steering the body's exhausted immune system, and the volume depleted patient, into dangerous waters.
Serum sickness is of itself a type of delayed allergic response. The most serious complications of serum sickness are nerve conditions such as Guillain-Barré syndrome, and peripheral neuritis.
Cross-reactions between penicillins and sulfa-drugs are common triggers of drug-induced GBS serum sickness, and fixed drug eruptions. It is also well documented that Cipro causes drug-induced serum sickness which can rapidly progress to Guillain-Barré syndrome. Bactrim has also been implicated high on the order of major offenders in drug-induced GBS. Medications with drug-induced reduction of oxygen intake also become possible or contributing factors, or underlying causes of Guillain-Barre Syndrome, but are often misdiagnosed or overlooked as a cause.
Vaccines, broad spectrum antibiotics, and "virus in stealth" (to help kill cancer cells) are themselves an onslaught on the immune system which can cause serum sickness leading to "provocation", the hallmark of the Guillain-Barré syndrome.
Guillain-Barré syndrome has 3 stages beginning with a progression phase over several days to several weeks, a plateau phase of similar duration, followed by a recovery phase over weeks to months. There are two forms of Guillain-Barré syndrome. In the acute form, muscle weakness develops rapidly; in the chronic form, muscle weakness develops gradually.
The symptoms of GBS vary a great deal from patient to patient, and so each can have a unique case history. The severity of symptoms can sometimes vary considerably between individuals. Lower back pain is an occasional initial presentation. Some cases may be so mild that medical attention is never sought, and there are case reports of patients who were only able to move a few fingers and wiggle some toes, retaining only a little motion in some fingers and/or a foot.
In the initial stages, the patient is likely to have few if any symptoms (Hughes, 1995). The clinical features of GBS range from asymptomatic to life threatening. A person experiencing a mild case of GBS may only have slight weakness or numbness and may not require hospitalization or treatment. Such a set of symptoms may represent a relatively mild form of GBS. In contrast, at the other extreme the patient may become totally paralyzed and fraught with complications.
As the syndrome progresses cranial nerves may also be involved, most commonly the facial and bulbar nerves, and in 25% of cases the "innervation of the respiratory muscles is so severely effected the patient requires ventilatory support" (Hughes, 1993, p. 176).
Symptoms may not appear immediately after the triggering mechanism: weeks may pass before the first signs of GBS appear. Between 1-3 weeks prior to the onset of weakness, 2/3 of patients have a history of gastrointestinal or respiratory infection. In very serious cases, the entire body can be paralysed, even including the eye muscles. GBS can be devastating because of its sudden and unexpected onset.
GBS may develop over the course of hours or days, or it may take up to 3 to 4 weeks. In the month or so before the syndrome’s appearance, patients most often have had a respiratory or gastrointestnal infection. Patients usually present a few days to a week after onset of earliest.
Acute illness of any sort precedes Guillain-Barré Syndrome in approximately two thirds of patients, and that incubation of the syndrome may be up to 6 weeks. But the average time between acute illness and onset of GSB is 11 days (Ropper, Wijdicks and Truax, 1991). Apart from most cases of GBS, surgery may also precede the syndrome (Bradley, 1974).
A recent history of increasing or diffuse muscle weakness and paralysis may indicate Guillain-Barre syndrome, especially if there was a recent illness.
Guillain-Barre syndrome (GBS) is characterized by weakness which affects the lower limbs first, and rapidly progresses in an ascending fashion. Limb weakness in GBS is nearly always bilateral (Parry, 1993).
Symptoms of GBS often start with tingling or numbness in the extremities of the body. The hands, feet, and face are often affected first.
Healthy nerves are wrapped in an outer coating known as myelin which is similar to the plastic insulation wrapped around a wire. In cases of GBS, the myelin is damaged, and without this coating, the nerves can no longer send messages or they send weaker messages, which may result in muscle weakness, tingling, numbness, or paralysis.
Early symptoms may include pain suggestive of nerve root irritation and paraesthesia of the legs and feet. Patients generally notice weakness in their legs, manifesting as "rubbery legs" or legs that tend to buckle, which may cause the patient to pull or fall in one direction or another due to unsteadiness, resulting in difficulty ambulating. Only about 28% of patients with the GBS remain able to walk unaided. Patients with the hyper acute form of the syndrome lose the use of their legs within a day.
The lower limb is often ischemic in diabetes. Fecal impaction as a cause of acute lower limb ischemia is reported in PubMed.
GBS is associated with prominant involvement of the speech and swallowing muscles and suppression of the gag reflex due to swallowing difficulty with alterations in speech patterns or dysarthria attributed to muscle paralysis. Involvement of facial, oropharyngeal, and ocular muscles results in facial droop, dysphagia and dysarthria.
A person with GBS may sometimes feel funny sensations (peripheral pulses) in their skin, or tingling— This is because the nerves that transmit messages about sensation are not working properly.
Vocal cord paralysis is a prominent finding in patients with GBS and there can be a slight to dramatic voice change as the vocal chords become affected. Speech may be unintelligible, "slurred" or whispery, as the various muscles required to form speech are weakened. Patients often appear to be nauseated and in a state of total exhaustion, marked by a "haggard appearance". Feeling unusually "cold" with chilly feelings is a common finding in many subjects with GBS.
Respiratory muscle paralysis in GBS can be life-threatening. In frail patients, as respiratory rate decreases, the patient becomes increasingly sedated.
GBS can freeze the breathing muscles with assault on muscle function and weakening of the diaphragm, resulting in episodic and paroxysmal disorders and respiratory failure with progression. Snoring, sleep apnea, cheyne stokes breathing and gasping for breath are part of the same problem.
Breathing may become laboured and difficult; laboured breathing is the hallmark of respiratory distress and respiratory failure due to paralysis of the diaphragm. Patients with neuromuscular disorders have rapid shallow breathing secondary to severe muscle weakness; difficulty with protruding tongue and difficulty swallowing indicate that bulbar involvement is significant and ventilatory failure is imminent, which requires that these patients be placed on ventilators in order to breathe.
Look at the shape of the neck. Adults and older adolescents having short thick necks are at greater risk of developing obstructive sleep apnoea. Aspiration and respiratory failure are major concerns.
Careful monitoring is very important during the early stages of GBS because breathing problems and other life-threatening complications can occur within 24 hours after symptoms first develop.
Objective findings of sensory loss tend to be minimal and variable in most cases. Sensory loss, if present, takes the form of proprioception (loss of sence of one's own perception of the relative position of neighbouring parts of the body to each other), which is occasionally impaired spontaneously, especially with extreme fatigue, resulting in abnormal or distorted postures indistinguishable from opisthotonus (where the head and heels are bent backward and the body is bowed forward), and which may also mimic dystonia.
GBS may herald an onset of sleepiness in a subset of patients, presenting with mild to moderate fatigue, to sleep drunkenness in which the patient often appears to be "sedated" due to extreme somnolence. Fast onset of fatigue in which patients often complain of being "very tired" is a common symptom in patients with Guillain-Barré Syndrome and can be one of the most disabling symptoms. Increased sedation is ALSO a serious side effect of many pharma agents.
GBS causes weakness in the legs, arms, and other muscles that can rapidly progress to complete paralysis. It is characterized most commonly by symmetric limb weakness and loss of tendon reflexes (areflexia), although the tendon reflexes, evidenced by muscle stretch reflexes, indistinguishable from tardive dyskinesia, may still be preserved in the first hours of the illness. As the weakness progresses upward, the arms and facial muscles also become affected, and fail to work.
Facial muscles control emotions. Weakness of facial muscles produces a characteristic haggard appearance, or a deceptively disinterested facial expression. The characteristic appearance of a "haggard" or "mournful" face is caused by facial muscle paralysis, and drooping eyelids. Further, when put on a fast or a restricted diet causing a steady reduction in weight, in the course of three or four weeks the patients will begin to show a haggard appearance.
Looking exhausted and unwell, the typical GBS patient presents with a variety of complaints 2-4 weeks after a relatively benign respiratory or gastrointestinal illness. The constilation of symptoms in GBS are marked general malaise, loss of appetite, nausea, vomiting and stomach pain, accompanied by weakness, tired feeling, and chills. Fever is low-grade or absent at onset. In certain cases there may also be evidence of brain involvement indicated by lethargy and migraine headaches.
Symptoms generally begin in the patient's feet, hands or face, spread to the legs or arms, and increase in intensity as they move towards the center of the body. They generally appear on both left and right sides of the body. However, GBS is unpredictable, and cases have been reported in which this "glove and stocking" pattern is not followed. Instead, motor symptoms or disruptions in the autonomous system may be observed. GBS may affect an arm or a leg alone, without spreading to the rest of the body. Further, hypertensive encephalopathy manifesting as status epilepticus before the onset of motor symptoms has occasionally been observed.
Weakness caused by GBS may occasionally be accompanied by pain and muscle spasms. Stiffness and cramping pain in GBS is not uncommon. Urinary retention and paralytic ileus may also be observed. Deafness is unusual but has been reported. The skin may become pale and dry, and sweating may become reduced. Fever should not be present, and if it is, another cause should be suspected.
Symptoms of GBS get worse very quickly. In the early stages, axonal neurophysiology may represent reversible axonal dysfunction rather than degeneration. It may only take a few hours to reach the most severe symptoms. Axonal neuropathies have multiple causes.
Reflexes are absent or hyporeflexic early in the disease course and represent a major clinical finding on examination of the patient with GBS.
CNS pathology is frequent in patients with GBS. It involves axons with secondary myolin impairment, microglial activation and inflammatory infiltration. Other variants are notable for an axonal pattern of electrodiagnostic findings and axonal pathology with little inflamation. After neurologic symptoms occur, patient history may reveal the sudden onset of altered levels of consiousness, ranging from lethargy or drowsiness to stupor.
GBS may rapidly evolve to a pseudo-coma-like state resembling acute unconsciousness, but with self-awareness preserved. Tachycardia and hypertension are an indication of awareness and/or pain. Fulminant cases of total body paralysis with loss of all cranial nerve reflexes have been described, whereby patients appear to have lost all central nervous system function, and other descriptions have been reported with a rapid deterioration evolving to a clinical state "resembling brain death".
GBS is one of the few neurological diseases whose clinical manifestations may mimic, or otherwise appear to be identical to those in brainstem death, illustrating an extreme polyneuropathy.
Although ascending paralysis is the most common form of spread in GBS, several variants of GBS are recognized and clinically similar states leading to catastrophic decline have been reported to occur with a variety of drugs and biologics. These disorders share similar patterns of evolution, recovery, symptom overlap, and probable immune-mediated pathogenesis. GBS, untreated, can rapidly lead to respiratory distress syndrome, sepsis, pneumonia, pulmonary emboli, and cardiac arrest.
A few people have an unusual problem with their autonomic nervous system that causes their blood pressure and pulse to fluctuate greatly; this, too, requires special treatment.
Patients who have, or are suspected of having GBS should be monitored closely for changes in blood pressure, heart rate, and other arrhythmias. Both high and low blood pressure as well as unusually slow or rapid heart beats can occur, and blood flow tends to be slow.
* cardiac arrhythmias
* labile BP
* abnormal haemodynamic response to drugs
* ECG abnormalities
* pupillary dysfunction
* sweating abnormalities
* urinary retention
* GI dysfunction
* blood volume and electrolyte disturbances are common due to loss of autonomic control of systemic blood flow distribution.
* Acute motor axonal neuropathy (AMAN) marked by diffuse weakness refers to the cases showing only motor symptoms; attacks motor nodes of Ranvier and is more prevalent in China and Mexico. The disease may be seasonal and recovery is rapid. Anti-GD1a antibodies are present. In the early stages, axonal neurophysiology may represent reversible axonal dysfunction rather than degeneration. Severe axonal GBS will show diffuse loss of sensory and motor responses with widespread active denervation. Diffuse weakness may lead to respiratory insufficiency.
* Acute motor sensory axonal neuropathy (AMSAN) is similar to AMAN but also affects sensory nerves with severe axonal damage. Severe axonal GBS will show diffuse loss of sensory and motor responses with widespread active denervation. Other variants are notable for an axonal pattern of electrodiagnostic findings and axonal pathology with little inflammation. Recovery is slow and often incomplete.
* Also known as: infectious polyneuritis, polyradiculoneuropathy, radiculoganglionitis, Landry's syndrome, Landry-Guillain-Barré syndrome, Landry-Kussmaul syndrome, Kussmaul-Landry syndrome, and Glanzmann-Saland syndrome (misnomer).
* Miller Fisher is one of the regional variants of Guillain-Barré syndrome, characterised by ophthalmoplegia, ataxia and areflexia, and is marked by paralysis of the eye muscles, abnormal muscle coordination, and absence of tendon reflexes. MF is primarily associated with accute idiopathic ophthalmoplegic neuropathy.
Miller Fisher variant (MF) is unique in that this subtype begins with cranial nerve deficits, most commonly the facial nerve. Facial weakness may precede other neurological findings. It is often unilateral and may be indistinguishable from Bell's palsy. Unilateral 3rd cranial nerve palsy is a rare manifestation of the Miller Fisher syndrome.
Fisher syndrome is characterised by impairment of eye movements (ophthalmoplegia), abnormal co-ordination (ataxia), and loss of tendon reflexes (areflexia). Guillain-Barré syndrome can, very rarely, present with coma and absent brainstem reflexes. These patients are NOT brain dead; their brains and sense of hearing and smell work perfectly well and the patient is alert and conscious of what is going on around him or her. But he/she may literally not be able to move a muscle in response. Although patients with GBS in the setting of preserved consciousness may appear to be completely obtunded, they are technically awake, and fully lucid, and can hear and understand what is going on around them. They only appear to be unresponsive, with a seemingly apparent reduction in alertness and arousal, due to a severely paralysed motor function.
The de-efferented state, in which a person has lost most if not all motor behavior, can occur with several conditions. Diffuse neuromuscular dysfunction as with myasthenia gravis (myasthenic crisis or overmedication with cholinesterase inhibitors) and diffuse polyradiculoneuropathy (the Guillain-Barre syndrome) including porphyria can make a patient behaviorally unresponsive, although s/he may be perfectly lucid with respiratory support. The history and presentation of these disorders are such that the patient is unlikely to be considered comatose.
Miller Fisher-Guillain-Barré overlap syndrome is a postinfectious allergic reaction involving both peripheral nerves in the cranium and neuraxis in the spinocerebellar tract. Bulbar weakness and difficulty handling secretions and maintaining an airway may be observed. Other signs may include cerebellar syndrome, hyporeflexia, and hypotonia.
MF syndrome is a rare acquired nerve disorder characterized by disproportionate involvement of cranial nerves and the presence of cerebellar signs, which shares many clinical features of the Guillain-Barré syndrome. It can occur in more limited forms and can even overlap with the Guillain-Barré syndrome. People who get GBS usually spend time in the hospital. But most people with GBS recover and are able to return to normal lives and activities.
Unlike Guillain-Barré syndrome, Fisher syndrome does not cause limb or respiratory muscle weakness. In Western countries Fisher syndrome represents between 5 and 10% of GBS cases. A further variant of GBS, Bickerstaff's brainstem encephalitis, is associated with upper motor neuron signs and disturbance of consciousness.
Bickerstaff’s brainstem encephalitis (BBE) is characterized by acute onset of ophthalmoplegia, ataxia, disturbance of consciousness, hyperreflexia or Babinski’s sign (Bickerstaff, 1957; Al-Din et al.,1982).
Bickerstaff’s brainstem encephalitis (BBE) , Fisher syndrome (FS) and Guillain-Barré syndrome (GBS) are similar clinically; BBE and FS were proposed to be the variant of GBS. Research in recent years has concentrated in identifying the antibodies that are thought to be responsible for GBS etc. It has been confirmed clinically that MFS, GBS with ophthalmoplegia, BBE, and another condition called acute ophthalmoparesis* are closely related, forming a continuous spectrum. This is supported by immunological findings with the antibody anti-GQ1b IgG being the common factor. [J Neurol Neurosurg Psychiatry 2001 Jan;70(1):50-55] This antibody is not found in other GBS patients so it is thought that it is responsible for the ophthalmoplegia. *Acute ophthalmoparesis (AO) is characterised by acute onset of paresis of the extra-ocular muscles without ataxia or areflexia.
The scientific literature also describes Bickerstaff's encephalitis as a syndrome of prodromal malaise and midbrain disturbances with almost complete suppression of all functions related to brainstem innervation. Bickerstaff's brain stem encephalitis shares many clinical features of MFS/GBS but also includes altered consciousness and signs of Central Nervous System (CNS) inflammation. Any of these variants may overlap since they all share a commonality with negative anti-GQ1b IgG antibodies. Raised cerebrospinal fluid protein is usually seen.
It has been postulated that the Miller Fisher syndrome was caused by brainstem encephalitis. It is true that the syndrome can be mimicked by a brainstem lesion, but typical cases of Miller Fisher syndrome rarely show any evidence of brainstem abnormalities either radiologically or during post-mortem examination. When clinical or radiological brainstem abnormalities are found, the condition may be referred to as Bickerstaff's syndrome or Bickerstaff's brainstem encephalopathy (or encephalitis) (BBE).
Patients in this group have ophthalmoplegia (external and internal) and ataxia. Upward gaze and horizontal gaze disability, pupillary abnormalities and nystigmus are frequent displaying complete internal and external ophthalmoplegia, compatible with typical BBE. Other clinical features of BBE are characterized as facial weakness, blepharoptosis, bulbar palsy and long-tract sensory disturbance (Susuki et al., 2003).
Patients with the pharyngeal-cervical-brachial variant (PCB) of Guillain-Barre syndrome (GBS) have anti-GT1a IgG with or without GQ1b reactivity, whereas those with Miller Fisher syndrome (MFS) or Bickerstaff's brainstem encephalitis (BBE) have anti-GQ1b IgG antibodies which cross-react with GT1a. The presence of a common autoantibody (anti-GT1a IgG) and overlapping illnesses suggests that PCB is closely related not only to GBS but to MFS and BBE as well.
Most sufferers make a complete recovery, though some are left with a permanent weakness, depending on the cause. Some varieties can exhibit recurring symptoms.
According to a Cochrane review abstract and plain language summary prepared and maintained by The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews 2007 Issue 2, Fisher syndrome always and Bickerstaff's brain stem encephalitis usually recovers completely.
Associated Signs & Symptoms:
Onset: Mean 40 years of age; Seasonal: High freequency in Spring (March to May).
Up to one third of patients require mechanical ventilation during the course of their illness. Causes for this include cranial nerve involvement affecting airway maintenance and respiratory muscle paralysis. Low oxygen saturation may be present with advanced respiratory muscle involvement. Other cranial nerves are effected and noticeable features are dysphagia, dysarthria, and facial diplegia, which can be seen in more than 50% of cases (Parry, 1993).
* Breathing difficulty (respiratory failure)
* Sucking in food or fluids into the lungs ( aspiration )
* Increased risk of infections
* Deep vein thrombosis
* Permanent loss of movement of an area
* Contractures of joints (onset)
Additional symptoms that may be associated with this disease:
* Blurred vision.
* Difficulty moving face muscles.
* Palpitations (sensation of feeling heartbeat).
* Difficulty beginning to urinate.
* Feeling of incomplete bladder emptying.
* Incontinence (leaking) of urine.
* Muscle contractions.
Typical symptoms include:
* Muscle weakness or paralysis (the most common symptom) or uncoordinated movements.
* Weakness begins in the feet and legs and may progress upward to the arms and cranial (head) nerves.
* May progress rapidly over 24 to 72 hours.
* May begin in the arms and progress downward.
* May occur in the arms and legs at the same time.
* May occur in the cranial nerves only.
* May not occur (mild cases).
* Sensation changes.
* Numbness, decreased sensation.
o Tenderness or muscle pain (may be a cramp-like pain).
o Usually accompanies or precedes muscle weakness.
Symptoms indicating an emergency:
o Difficulty swallowing, drooling.
o Difficulty breathing.
o Breathing absent temporarily (apnea).
o Feeling "unable to take a deep breath".
Several disorders, such as acquired hypokalemia, myasthenia gravis, periodic paralysis, and poliomyolitis, have symptoms similar to those found in GBS. The uncommon Miller-Fisher variant of Guillain-Barré syndrome resembles Botulism. The syndrome causes weakness through demyelination of the peripheral nerves. Like botulism, the Miller-Fisher variant preferentially strikes cranial nerves, but with the additional sign of ataxia. Early symptoms may include fever, headache, and sometimes, pneumonia. They are followed by facial paralysis, diplopia, external ophthalmoplegia, and paresthesia of the arms and trunk.
Intravenous immunoglobulin (IVIg) and plasma exchange are often used as treatments in this patient group. Treatment modalities include anticoagulation, IVIG, plasmapheresis (a procedure in which antibodies are removed from the blood) and high dose corticosteroids.
Although the efficacy has not been clinically proven, treatment of Miller Fisher syndrome is much the same as 'classic' GBS though the different symptoms require modified management with emphasis on the eyes. Intravenous immunoglobulin or plasma exchange treatment is likely in all but the mildest cases. The chances of recovery are usually good.
It is also very important to treat the risks of respiratory failure, autonomic abnormalities and venous thromboembolism, which Hughes, 1995, reports can cause death in up to 12% of patients with Guillain-Barré Syndrome. While most patients with Guillain-Barré Syndrome attend hospital, only one third require intensive care (Hughes, 1995). For respiratory failure, artificial ventilation is required, and Parry, 1993, reports this is used in up to 25% of patients.
Parry, 1993, describes "the best quality supportive care" as the cornerstone for the treatment of Guillain-Barré Syndrome, no matter what advances have been made in treatment for the disease itself.
A case where cerebral edema and ophthalmoplegia was reversed with administration of mannitol is reported in the literature.
Transient diabetes has also been observed in certain cases of GBS. Some drugs have even been reported to trigger diabetes in patients with no previous history of diabetes. In fact, ophthalmoplegia is a common cranial neuropathy in both the Miller Fisher variant of GBS, and in Diabetes Mellitus. In case of 3rd nerve involvement, usually unilateral extra ocular musces are affected.
In ophthalmoplegia associated with diabetes, ischemic nerve involvement may lead to nerve infarction. Diabetic ketoacidosis associated with Guillain-Barré syndrome with autonomic dysfunction has also been reported in the literature. Paralysis of the bladder is also a common symptom of this type of neuropathy.
Cerebral edema can also occur unpredictably in this patient group, especially from rapid electrolyte correction. The association between Guillain-Barré syndrome and diabetes stems from the fact that both have auto-immune mechanisms which may share a common inciting event. Notably, transient diabetes, especially hyperglycemia, and Guillain-Barré syndrome can be drug-induced, demonstrating that there may be some overlap between these two types of neuropathies, for example.
Clearly, both disease and treatment are related to each other, and there may be some overlap between them, which requires a high index of suspicion.
Coagulopathy in Guillain-Barré syndrome may present with an elevated fibrinogen level and is typically elevated at presentation. Fibrinogen, is a blood-clotting protein found in circulating blood. The plasma fibrinogen level appears to reflect disease activity in acute Guillain-Barré syndrome. Ongoing activity of Guillain-Barré syndrome may be reflected by a persistently elevated fibrinogen level and thus, may be the basis for relapse. Notably, blood borne infections lyse easily in the presence of fibrinogen.
Many secondary complications that follow GBS include deep vein thrombosis, anemia, and mild to moderate migraine attacks, which may encompase a wide range of adversities. Blood volume and electrolyte disturbances are common due to loss of autonomic control of systemic blood flow distribution. A higher than normal fibrinogen level in the presence of D-dimer is the hallmark of thrombosis, indicating that blood thinners may be needed to prevent blood clots.
Many drugs have been known to trigger a procoagulation response, and many drugs are highly bound to proteins in blood (91-99%); many of them have a half life that can potentiate or even interact with other medications.
CSF and electrodiagnostics may be useful, but because of the acute nature of the disease, they may not become abnormal until the end of the first week. The diagnosis of Guillain-Barre syndrome is also based on clinical features and albumin cytological dissociation present in the spinal fluid.
CBC shows leukocytosis and a shift to immature forms early in the illness. Cases of Guillain-Barre syndrome can have pleocytosis, or CSF granulocytes. The presence of polymorphonuclear granulocytes does not rule out the diagnosis of GBS". Eur J Neurol 10(5): 479-86.
If the total WBC is high due to a rise in neutrophils and eosinophils, then an allergic, or parasitic process is most likely. Neutrophils, are also known as "segs", "PMNs" or "polys" (polymorphonuclears). They are the body's primary defense against bacterial infection and also reflect the degree of physiologic stress.
Neutrophilia may be due to a number of acute and chronic causes such as infection, inflammation, emotional stimuli, drugs, metabolic, hormonal, and endocrine disturbances, including hematologic abnormalities.
Further, it is always possible to have two or more conditions or diseases rather than just one. For many diseases, there are usually other disorders that are related to it, or associated with it, confounding the clinical picture. Underlying conditions cause the disease and complications are usually caused by the treatment.
Two conditions may be caused by a single underlying condition: for example, diabetes and hypertension may be related due to an underlying metabolic syndrome. Guillain-Barre Syndrome typically follows a respiratory or gastrointestinal illness, immunization, trauma, or 'metabolic insult'.
An underlying condition usually has the first disease as one of its symptoms or complications, but that does not nesessarlly mean that the first disease has advanced, or that a given secondary disorder or condition is irreversible, or that care would be a futile waste of healthcare resources.
The bald truth is that many neurological complications have iatrogenic causes.
All drugs are poisons (potentially) and all poisons are medications: drug side effects ranging from the annoying to the lethal, marked by oversedation, respiratory depression and hypotension. There is also a physical tolerance and withdrawal syndrome (excitement seizures), and a panic factor marked by sudden onset of intense apprehension or fear and impending doom with awareness which can kill you. Panic can result in significant hemodynamic instability. Adrenaline raises the blood sugar glucose level. A panic attack in severe GBS is capable of producing airway obstruction. Tachycardia and hypertension are also an indication of awareness and/or pain.
Many drugs can potentiate and/or exascerbate similar or like-virtues of other medications known to cause respiratory depression.
Respiratory depression represents the principal negative variable introduced with conscious sedation and left unrecognized and untreated, is the cause of panic, including most serious complications.
Many drugs can mask the signs and symptoms of overdosage of other drugs or underlying conditions. Thus patients can have exascerbation of their condition(s) or underlying disorder(s).
Many drug can lead to changes in the blood-brain barrier (BBB), allowing an infectious agent to gain entry to the brain and produce lethal central nervous system (CNS = brain and spinal cord) infection. The scientific literature describe two bacterial factors specific to the meningitis pathogen that thwart the normal protective role of the blood-brain barrier, leading to serious infection. Spontaneous meningitis can kill in 24 hours if left untreated.
Bacteria invade the cerebrospinal fluid (CSF) by crossing the blood-brain barrier through a complex series of events, beginning with attachment of bacterial fibrils to the brain microvascular endothelial cells. Once in the CFS, bacteria multiply rapidly due to the absence of local defences where they further degrade the BBB and exascerbate tissue damage resulting in partial or permanent brain injury.
Many drugs, especially antipsychotics, inhibit dopamine nerve transmission in the frontal lobes and in the emotion-regulating limbic system of the brain. This inhibition is no different than surgical lobotomy. It is chemical lobotomy. The main impact of such drugs is to blunt and subdue the individual. They also physically paralyze the body, rendering the individual less able to react or to move. Thus they act as a chemical lobotomy and a chemical straightjacket. In some cases these types of drug can physically paralyze the intestines, vital organs, including the inspiratory muscles of the diaphragm (diaphragmatic paralysis) literally smothering the patient; which shares many clinical features of the Guillain-Barré syndrome.
Anti-emetics, especially phenothiazine derivatives that suppresses activity in the trigger zones of the vomiting center by "paralyzing the gastrointestinal tract" can inhibit gastrointestinal motility which can exascerbate gastrointestinal problems. GBS can also inhibit gastrointestinal motility via a similar mechanism, compounding the problem.
Turn the focus to drug-signature with emphasis on drug pattern recognition.
Many drugs can potentiate and mask the signs and symptoms of overdosage of other drugs or underlying conditions, ie. organic brain syndrome, etc. Thus patients can have exascerbation of their conditions.
Certain drugs are known to obscure the diagnosis and treatment of other conditions, ie. intestinal obstruction.
Don't be fooled into believing that all drugs are actually treating disease. Many of them are actually suppressing overall brain and vital organ function, while creating diseases and exascerbating illness.
An increased awareness among clinicians of drug-induced disorders should maximize their recognition and minimize the incidence of GBS.
GBS is virtually indistinguishble from many forms of drug overdosage and should always be considered in the differentials.
Some of the more prominant symptoms of drug overdosage include central nervous system (CNS) depression which may vary from simple lethargy to coma - two or more of the following may occur together: Falling levels of consciousness or coma; convulsions (seizures); fast or slow heartbeat; large fixed dilated pupils; palor; dry skin; weak pulse; low blood pressure; tachycardia; trouble in urinating; twitching or jerking movements; and vomiting. Other possible manifestations include paralytic ileus, hepatic dysfunction, renal dysfunction, gastrointestinal disturbances, respiratory depression (breathing difficulty), cardiac arrhythmias (heart failure), skin rashes, fixed drug eruption, dry eyes, and ocular gyric crisis (eyes rolling back into their orbits).
Symptoms of drug over-dosage include sedation, difficult breathing, swirling tongue movements or swelling of the tongue, difficulty swallowing, loss of consciousness or coma, hypotension, tachycardia, EEG changes, ventricular arrhythmias, including temperature dys-regulation can lead to hypothermia.
Body temperature can be marred by the effects of drug-induced temperature dys-regulation, which can suppress sweating, causing central nervous system impairment, often resulting in an afebrile state.
Neuroleptanalgesia (neurolept analgesia), also called "conscious sedation" refers to the use of major tranquilisersin conjunction with narcotics. Patient often gets a `locked-in' state of `outer calm inner panic' that under normal circumstances patients are able to recall vividly and unpleasnantly. The patient is technically awake, but under the influence of the drugs administered. Neurolept-analgesia, which is produced by the combination of an opioid and a tranquilizer is defined as a state of CNS depression.
ECG may suggest heart problems in some cases. Many different abnormalities may be seen, ie. 2nd and 3rd degree AV block, T-wave abnormalities, ST depression, QRS widening, including a variety of rhythm disturbances. All variants have in common absent or diminished tendon reflexes, elevated CSF protein concentrations, and electrodiagnostic abnormalities. ECG's may be marred by the effects of multiple pharmacological agents.
Marked blood pressure lability with alterations between hypertension and hypotension following paresis suggests an atypical course of GBS.
An electromyogram, or EMG, is used to ascertain nerve malfunction: it is a test of nerve conductivity, performed by running electricity through the patient and measuring the output at certain points.
Causes of death include adult respiratory distress syndrome, sepsis, pneumonia, pulmonary emboli, and cardiac arrest, usually secondary to the victim's level of care. In some cases, GBS deaths are attributed to cardiac arrest, while in others the cause appeared to be asphyxia due to failure of the cough reflex (actually the result of DRUG-induced muscle paralysis); cardiac arrest is a direct result of failure to place the patient on ventilatory support in a timely manner, or withdrawal of ventilatory support.
Although the clinical syndrome classically presents as a rapidly progressive acute polyneuropathy, several pathologic and etiologic subtypes exist. Most patients with GBS exhibit absent or profoundly delayed conduction in action nerve fibers. This aberrant conduction results from demyelination of nerve cell axons. Peripheral nerves and spinal roots are the major sites of demyelination, but cranial nerves also may be involved.
In a subset of patients, GBS is associated primarily with myelin-sparing axonal damage resulting from a direct cellular immune attack on the axon itself. The acute inflammatory demyelinating polyneuropathy (AIDP) subtype of GBS is by far the most commonly identified form in North America. It is generally preceded by an antecedent bacterial or viral infection. However, in one-third of GBS cases, the individual and his or her doctors can identify no triggering infection.
GBS is believed to result from an autoimmune response, both humoral and cell mediated, to a recent infection or any of a long list of medical problems. Its relation to antecedent infections and the identification of various antiganglioside antibodies suggest that molecular mimicry may serve as a possible mechanism for the disease. The antibodies formed against gangliosidelike epitopes in the lipopolysaccharide layer of some infectious agents have been shown in both necropsy and animal models to cross-react with the ganglioside surface molecules of peripheral nerves.
Nearly 40% of GBS patients are seropositive for Campylobacter jejuni. Lymphocytic infiltration and macrophage-mediated demyelination of the peripheral nerves are present. Symptoms generally resolve with remyelination.
Bradley, 1974, suggest that during any of the above illness or incidents, a viruses, bacteria or any other antigen enters the nerve's Schwann cell, and replicates. It is then that the macrophages are attracted to the antigen and begin processes that lead to demyelination that is the classic feature of Guillain-Barré Syndrome.
Parry, 1993; Hughes, 1995 and Bradley, 1974, all agree that the primary pathological change seen in Guillain-Barré Syndrome is the segmental demyelination of nerves, most effected being the nerve roots. Parry, 1993, and Hughes, 1995 note that macrophages are the primary cause of the degradation, but Bradley, 1974, and Weller and Cervos-Navaro, 1977, mentioned major degradation may occur without the presence of macrophages. Macrophages initially invade the basal lamina of the neurones, then penetrate and ingest the myelin lamellae and the nerve axon is gradually bared (Hughes, 1995).
Often demyelination is mild and axons are not damaged. In such cases, with the remyelination the neurones function is restored, and recovery can be complete. But in some cases demyelination is severe, and axonal degradation occurs as well, and it is then recovery of the nerves is limited (Weller and Cervos-Navaro, 1977).
Macrophage-associated demyelination confirms the diagnosis of acute inflammatory demyelinating polyneuropathy (Guillain-Barré syndrome). Histologically, nerves show infiltration by lymphoid cells, with phagocytosis of myelin by macrophages.
During the progressive phase of Guillain-Barré Syndrome the characteristic neurophysiological features are:
* Conduction block
* Conduction slowing
Conduction slowing occurs mainly in the spinal roots, terminal nerve segments and nerve trunks where the nerve may be compressed and terminal motor nerve branches (Hughes, 1995).
The initial changes described by Hughes, 1995; and Parry, 1993, are not seen until day three or later in the disease process, and when seen changes include diminished compound muscle action potentials which indicates conduction block, and is due to the terminal motor nerve involvement.
Not only is conduction blocked, but also combined with the inflammation, as nerve damage occurs, nerve conduction slows.
Parry, 1993 notes that nerve conduction study is used for diagnosis more commonly than examination of cerebrospinal fluid. But for the prognosis of Guillain-Barré Syndrome, needle EMG is of upmost importance, and both are very useful to help understand the physiological basis of Guillain-Barré Syndrome (Parry, 1993).
The risk of developing GBS or MFS may be higher after infection with specific C. jejuni types, depending upon factors specific to immune function and treatment modality.
All forms of GBS, although rare, are due to an immune response to foreign antigens, mistargeted to host nerve tissue, a form of antigenic mimicry. The targets of such immune attack are thought to be gangliosides, which are complex glycosphingolipids present in large quantities on human nerve tissues, especially in the nodes of Ranvier. An example is the GM1 ganglioside, which can be affected in as many as 20–50% of cases, especially in those preceded by Campylobacter jejuni infections. Parry, 1993, notes trauma of any sort may lead to Guillain-Barré Syndrome as they cause the release of myelin antigens into circulation.
Another example is the GQ1b ganglioside, which is the target in the Miller Fisher syndrome variant, Campylobacter jejuni has been identified as the predominant cause of antecedent infection associated with Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS).
Miller Fisher Syndrome (MFS) is a syndrome of ophthalmoplegia, ataxia and areflexia associated with acute idiopathic ophthalmologic neuropathy, manifests as a descending rapidly developing but reversible paralysis, proceeding in the reverse order of the more common form of GBS. It usually affects the ocular muscles first and presents as ophthalmoplegia, ataxia, and areflexia. GBS presents similarly in a somewhat reverse order.
At first the patient may become unresponsive to light, with sluggishly reactive pupils, which can quickly lead to fixed, dilated pupils with progression. There may be no verbal response, no motor response, and no occular response. The connection with GBS comes because some GBS patients develop paralysed eye muscles too. Consequently, Miller Fisher and Guillain-Barré syndromes can overlap. Physical findings include delayed pupillary light response, resting tachycardia, sinus arrhythmia, and orthostatic hypotension.
Autonomic dysfunction in GBS is manifested as tachycardia and mild hypertension in the acute stage and cardiac arrhythmias associated with autonomic dysfunction are a recognized manifestation in Guillain-Barré syndrome. The autonomic nervous system is responsible for the involuntary actions that regulate our heart, gastrointestinal, urinary, muscles, and bowel functions as well as our metabolic and endocrine systems. Endocrine responses include reactions to stress or the flight or fight response.
Autonomic neuropathy is a group of symptoms caused by damage to nerves that regulate blood pressure, heart rate, bowel and bladder emptying, digestion, and other body functions. Sinus tachycardia, (>90/min), is seen in over 35% of patients with Guillain-Barré Syndrome, and over 30% suffer from hypertension (Parry, 1993).
Dysautonomia, often causing profound swings in blood pressure (hypotension alternating with hypertension) are often conspicuous in patients with Guillain-Barré syndrome. Dysautonomia in GBS is usually acute and reversible.
Malignant hypertension due to autonomic dysfunction is also a known complication of Guillain-Barre syndrome.
Frequency of Autonomic Abnormalities in GBS.
Parry, 1993, p.15)
GBS impacts the muscles that control the bladder and colon, as a consequence of autonomic dysfunction, caused by damage to nerves that regulate blood pressure, heart rate (tachycardia), bowel and bladder emptying, digestion, and other body functions. Nerve signals can't pass to muscles. Severe forms of GBS may result in urinary or fecal incontinence. A history of grossly bloody stools may also be observed; fecal leukocytes are usually present. GI bleeding involves assessing hemodynamic stability, resuscitating the patient as needed, locating the source of the bleed, and treating the underlying cause
The end result of an autoimmune attack on the peripheral nerves is inflammation of myolin and subsequent conduction block, leading to a rapidly evolving flaccid paralysis with or without accompanying sensory disturbances.
Rapid correction of chronic hyponatremia can cause osmotic brain demyelination. Osmotic demyelination, is an iatrogenic disease related to inappropriately rapid correction of Salt and Water Disorders.
Constipation is often a problem, due to the reduced activity of the intestines, change of diet, weakened stomach muscles that resist efforts by the patient to express the intestinal content. Bowel and bladder dysfunction with intestinal muscle paralysis; constipation, obstipation and megacolon is a consequence of defect in the nerve supply of the colon. Certain medications can inhibit gastrointestinal motility (physically paralyze the intestines) which can exascerbate gastrointestinal problems.
A case study showed that patients with GBS had used anti-motility drugs and penicillin more often.
Headache in GBS is unusual, but has been reported. Irritated, inflamed or damaged nerves in the brain, spinal cord or body can cause headache with increasing severety, as can ophthalmoplegia associated migraine in the Miller Fisher variant as the disorder progresses. Pain syndromes of Guillain-Barré are neuropathic (the result of an injury or malfunction in the peripheral or central nervous system) as well as nociceptive in origin. Neuropathic pain is often caused by an injury, but this injury may not involve actual damage to the nervous system. Nerves can be compressed by tumours, strangulated by scar tissue, or inflamed by infection.
Acute inflammatory demyelination is a unique disorder simulating brain neoplasm. Acute inflammatory demyelinating lesions present as large masses that mimic brain tumors. Headaches and motor deficits are the most common presenting symptoms. Speach problems and motor deficits are the most common findings on physical examination.
Demyelinating disorders thus present with radiological features that mimic brain tumors, or may be the result of extreme intracranial hypertension. Brain demyelination can cause ring enhancement mimicking a neoplasm, or infection on routine imaging. This is a well known entity to neuropathologists who deal with many obscure pathological entities that may simulate brain neoplasms, such as infection (abscess), for example.
Because of demyelination, mass lesions mimic brain tumors on CT or MRI and may be misinterpreted as metastatic cancer of the brain. However, demyelination, as evidenced by slow conduction velocity and conduction block, are reversible features of the disease.
What looks like damage from hypoxic ischemic injury on brain imaging, actually can be caused by concurrent "infection". CT scans may also be suggestive of structural damage to the brainstem in the form of decreased density. Abnormal lesions (high-intensity) with clinical symptoms are compatible with typical BBE. These MRI signals may move and regress with the clinical course of the illness (Mondéjar et al., 2002).
Weakness Vs. Atrophy
Guillain-Barré syndrome is a disorder caused by "nerve" inflammation (not muscle inflamation), involving progressive muscle weakness or paralysis, which must be differentiated from muscle damage or muscle wasting. GBS initially does not usually produce evidence of muscle inflammation or waisting such as elevation of Creatine Kinase (CK) concentration.
CK is an enzyme or type of protein found in muscle and brain that leaks out and is released into the bloodstream when muscle is damaged, may also be tested from the record. CK is the most sensitive enzyme and in the presence of most diseases, levels can be elevated as much as 50 to 100 times the reference range. The creatine kinase level usually parallels a disease activity. In normal conditions, there is very little creatine kinase circulating in the blood of the average, healthy human being.
Normal creatine kinase levels do not rule out significant neuromuscular disease, FIRSTConsult.
Muscle atrophy is seen late in the syndrome due to muscle weakness and disuse (Parry, 1993). In severe cases of GBS, muscle weakness develops so quickly that muscle atrophy doesn’t occur, but hypotonia and areflexia do. Weakness develops acutely and progresses over days to weeks. Severity may range from mild weakness to complete tetraplegia with ventilatory failure. Peak deficits are reached by 4 weeks after initial development of symptoms. Recovery usually begins 2-4 weeks after progression ceases.
Areflexia is noted in nearly all Guillain-Barré Syndrome patients and is due to large diameter muscle spindle afferent axon involvement, Parry 1993. Hypotonia in Guillain-Barré syndrome is common and can be observed with significant weakness. It is characterized by diminished resistance of the abdominal muscles, with diminished tone of the skeletal muscles; most notable for a "soft, non-tender abdomen". The abdominal muscles feel 'soft and doughy'.
Muscle wasting is a hallmark of a number of diseases, including cancer, bacterial sepsis, AIDS, diabetes, and end-stage heart, kidney, and obstructive pulmonary disease. Progression of skeletal muscle atrophy is one of the characteristic features in cancer patients. Even in paraneoplastic disorders the serum CK level typically is elevated 8-100 times normal. Persons with GBS or clinically similar disorders typically have normal or low CK levels at onset of the disease, unless tissue damage in the brain or elsewhere has already occurred.
The hallmark of muscle wasting (or muscle damage) is elevation of CK. The wasting away of fat and muscle (cachexia), is the most visible hallmark of metastatic cancer. Persons with cancer typically have high CK levels. Elevation of CK may be seen in stroke, extreme shock, and brain tumor(s) in which CK levels can sometimes temporarily go off the scale, topping out at 50,000 to 200,000 U/L, a sign of severe muscle fiber breakdown (necrosis). CK levels may rise significantly in about 2 to 3 hours.
Wasting of limb muscles is not an acute finding in Guillain-Barré syndrome. A clinical feature of demyelination is muscle weakness, "without muscle atrophy", marked by a normal CK level.
A normal CK at the time of a patient's admission would argue favorably against a diagnosis of structural brain damage or active metastatic cancer, for example.
Skeletal muscle atrophy is a common comorbidity of cancer. The progressive depletion of skeletal muscle is a hallmark of many types of advanced cancer. However, a clinical feature of demyelination is muscle weakness without muscle atrophy.
Hypokalaemic periodic paralysis has a predilection for thyrotoxicity in some patients. It is associated with a low potassium concentration and a normal creatine kinase level. Further, people who are predisposed to panic and anxiety attacks are also more prone to sleep paralysis.
Lyme disease may also cause weakness secondary to peripheral neuropathy but it also does not produce evidence of muscle inflammation, such as elevation of the CK. Putting aside the issue of whether Lyme disease does or does not cause some cases of Guillain-Barre syndrome, the two diseases share so many symptoms that Lyme disease can easily be mistaken for Guillain-Barre syndrome.
Global encephalitis has been also been proposed to explain the encephalopathy that occurs most commonly in small cell lung cancer. However, the encephalopathy may be secondary to multidrug therapy and sometimes radiation therapy.
Another possible form of paraneoplastic encephalitis is limbic encephalitis, characterized by anxiety and depression, leading to agitation, confusion, and behavioral abnormalities.
Guillain-Barré syndrome is a disorder caused by "nerve" inflammation involving progressive muscle weakness or paralysis, which must be differentiated from muscle damage, or muscle wasting. GBS does not usually produce evidence of muscle inflammation or waisting, such as elevation of Creatine Kinase (CK) concentration.
CK is an enzyme or type of protein found in muscle and brain that leaks out and is released into the bloodstream when muscle is damaged, may also be tested from the record. CK is the most sensitive enzyme and in the presence of most diseases, levels can be elevated as much as 50 to 100 times the reference range. The creatine kinase level usually parallels a disease activity. In normal conditions, there is very little creatine kinase circulating in the blood of the average, healthy human being.
Muscle wasting is a hallmark of a number of diseases, including cancer, bacterial sepsis, AIDS, diabetes, and end-stage heart, kidney, and obstructive pulmonary disease. Progression of skeletal muscle atrophy is one of the characteristic features in cancer patients. Wasting of limb muscles is not an acute finding in Guillain-Barré syndrome.
HIV can cause Guillain-Barré syndrome early in the infection, and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) later in the course of AIDS. Many different medical and physical conditions have been implicated as antigenic triggers for autoimmune GBS. All of them have been attributed to an 'exhausted immune system' that has absolutely nothing to do with AIDS.
The four clinical AIDS symptoms are identical to those associated with conditions that run rampant on the African continent such as malaria, tuberculosis, parasitic infections, the effects of malnutrition and dysentery. Campylobacter jejuni in Waterborne Protozoa (parasites) and possibly many other infectious processes may also produce an AIDS-like picture.
T-cells (lymphocytes), which are mediators of immune function are also involves in the pathogenesis of most or perhaps all forms of Guillain-Barré syndrome. Symptoms generally coincide pathologically with various patterns of lymphocytic infiltration.
Molecular mimicry occurs when an invading pathogen is structurally similar to host cells in order to escape immune detection, which results in the immune system confusing the pathogen with 'self' cells. When the host produces an immune response to such an invading pathogen, this response inadvertently begins attacking host cells using these same T-cells and antibodies primed by the initial infection with the mimicking pathogen, which may "mimic" virtually any neurological disease process.
T-cell sensitization causes loss of myelin which disrupts nerve impulses resulting in loss of neurotransmission to the periphery. GBS can occur in patients with severe T-cell suppression (T-cells literally become worn out) as a consequence of incomplete recovery following infectious or chemotherapeutic agents, especially radiation which preferentially suppress T-lymphocyte responses. Thus lymphocytopenia and incomplete recovery is consistent with immunocompromise in patients with GBS. This form of " lymphocytopenia" is often confused with the disease of the same name that results in immuno-deficiency.
After a brief period following radiation therapy, demyelination is seen histologically and is associated with mononuclear cells. The extent of demyelination is related to the radiation dose, fractionation methods, and the portals used.
The flaccid phase in GBS may be overthrown by an inadvertent generation of mutant T-cell receptors that are anti-self, marked by an AIDS-like super-immune response sending white blood cells (called T cells) rampaging through the body destroying its own tissues. Chronic anxiety, stress, depression and panic, have all been shown to compromise health, damage immune function, and result in symptoms almost or identical to AIDS, often resulting in questionable diagnosis.
Mental stress provokes production of the hormone cortisol; excessive cortisol also causes rapid and dramatic reductions in T cells. Within minutes, stress induces cortisol levels to increase as much as 20-fold.
High levels of cortisol can eventually cause what medical texts describe as "significant 'atrophy' of all the lymphoid tissue throughout the body" which may lead to "fulminating infection and death from diseases that would otherwise not be lethal."
Overuse of laxitives, or in combination with bisphosphonate, or magnesium sulfate, used to treat severe constipation can lead to hypermagnesemic pseudocoma, which mimics a central brainstem herniation syndrome. Hypermagnesemia may occur during therapy with any bisphosphonate. The most common adverse events associated with the administration of sodium biphosphate and sodium phosphate are self-limiting flu-like symptoms related to an acute-phase reaction.
Epsom salt has also been used for numerous ailments including abdominal pain, constipation, sprains, muscle strains, hyaline membrane disease, and cerebral edema. Epsom salt is essentially 100% magnesium sulfate.
Potential sources of excess magnesium intake include antacids, laxatives, cathartics, and parenteral administration. Clinically, hypermagnesemia resembles Lambert-Eaton syndrome. Severe hypermagnesemia may also mimic brain death.
Acute paralysis in Guillain-Barre syndrome is related to a Na negligence. It results from a deficit of sodium, or surplus of water. It occurs in patients with Guillian Barre syndrome, meningitis, encephalitis, pneumonia, septicemia, severe malaria, bronchiolitis, RSV infection, and clinical insult.
Na (sodium): Na is the chemical symbol for sodium. From natrium, a synonym for sodium. Normal blood sodium level is 135 - 145 milliEquivalents/liter (mEq/L), or in international units, 135 - 145 millimoles/liter (mmol/L).
Rapid rate IV infusion could cause fluid or drug overload.
Hyponatremia results from a deficit of sodium, or surplus of water. It occurs in patients with meningitis, encephalitis, pneumonia, septicemia, severe malaria, bronchiolitis, RSV infection, and Guillian Barre syndrome. Rapid correction of hyponatremia can cause osmotic brain demyelination. Osmotic demyelination is an iatrogenic disorder related to inappropriately rapid correction of Salt and Water Disorders. Signs of fluid overload include tachycardia, elevated blood pressure, ascites, dyspnea and other signs of respiratory distress.
Hyponatremia is a metabolic derangement that occurs principally in patients with hyperglycemia, caused by high levels of glucose in adult-onset diabetes. Untreated hyperglycemia can rapidly progress to hyperglycemic hyperosmolar nonketotic syndrome, resulting in osmotic brain demyelination. Osmotic demyelination is an iatrogenic disorder related to hyponatremia, due to inappropriately rapid or negligent correction of Salt and Water Disorders.
The symptoms of hyponatremia can mimic the symptoms of dehydration, the direct opposite of hyponatremia. It is also known as hyperhydration.
There is a positive association between blood brain barrier disruption, and osmotically-induced demyelination, by exposing substances normally excluded from the brain. Active demyelination is accompanied by transient breakdown of the blood-brain barrier. If you're going to deliver drugs by disrupting the blood-brain barrier, you're going to let in everything else in the bloodstream, including purulent matter.
Any breach in the BBB can lead to alterations in the CNS (central nervous system), with possible induction of blood-borne infection leading to meningitis. Blood-brain barrier (BBB) disruption is accompanied by cerebral edema.
Septic shock can occur when bacteria leave the original site of an infection — most often in the lungs, abdomen or urinary tract — and enter the bloodstream. The bacteria then produce toxins that affect your blood vessels, leading to a profound and life-threatening decline in blood pressure.
Bacteria invade the cerebrospinal fluid (CSF) by crossing the blood-brain barrier through a complex series of events, beginning with attachment of bacterial fibrils to the brain microvascular endothelial cells. Once in the CFS, bacteria multiply rapidly due to the absence of local defences where they further degrade the BBB and exascerbate tissue damage resulting in permanent brain injury.
Brain injury caused by drug induced meningitis related inflamation, edema, reduced blood flow (ischemia), or endogenous toxins can lead to neurologic sequalae, including deafness, mental retardation, motor dysfunction, and (secondary) epilepsy. An "inferior ischemia" implies that there may not be enough oxygen in the blood to sustain vital organs.
Metabolic impairment causes demyelination or axonal degeneration. Axonal degeneration secondary to severe demyelination may mimic brain death. Similarities may be found in all demyelinating syndromes.
Diabetes insipidus (DI) is a condition characterized by excretion of large amounts of severely diluted urine, which cannot be reduced when fluid intake is reduced. It denotes inability of the kidney to concentrate urine. Symptoms of diabetes insipidus are quite similar to those of untreated diabetes mellitus. Signs of dehydration may also appear in some individuals since the body cannot conserve much (if any) of the water it takes in.
Diabetes Insipidus in GBS is caused by a nervous derangement. Overworked emotions associated with 'fear' (panic factor) is the cause in those who are very nervous. Certainly the inability to breathe properly can be alarming, and many persons will immediately react with anxiety, fear, or panic. While severe anxiety, fear and even panic may accompany the progressive phase, severe depression and fatigue often cloud recovery.
Adults with untreated DI may remain healthy for decades as long as enough water is drunk to offset the urinary losses. However, there is a continuous risk of dehydration.
A more common are acquired forms of DI is Nephrogenic diabetes insipidus, which occurs as a side-effect to some medications, and/or electrolyte disturbances, such as hypokalaemia.
Dipsogenic DI is due to a defect or damage to the thirst mechanism, which is located in the hypothalamus. This defect results in an abnormal increase in thirst and fluid intake that suppresses ADH secretion and increases urine output.
The effects of many sedative and anesthetic agents can closely mimic brain death. All the so-called major tranquilizers can mimic a death-like condition by causing reduced brain wave activity and lack of responsiveness.
CAVEAT: Encephalopathy with peripheral neuropathy may falsely mimic brainstem death.
Drug intoxication may cause a deep physiologic depression that resembles brain death, and drug intoxication is the most common cause of coma of rapid onset which may mimic brain death. The examination can be marred by the effects of sedation.
Metabolic derangement and endocrine crisis can also mimic brain death. Severe hypermagnesemia may also mimic brain death. There may be other conditions that mimic brain death, or that provide examples of the mistaken diagnosis of brain death.
Brain death is defined as the irreversible cessation of function of the entire brain with three specific criteria: 1) coma, 2) absent brainstem reflexes and 3) apnea. In addition to these clinical criteria, there are important prerequisites: 1) NO intoxication or poisoning, 2) NO core temperature greater than 32 degrees Celsius, 3) clinical or neuroimaging evidence of acute central nervous system catastrophe and 4) absence of confounding medical conditions such as severe electrolyte, acid-base, or endocrine disturbances.
Although many conditions can mimic brain death clinically upon examination, without excluding them you will KILL a person by homicide, or criminal negligence, despite the reversibility of brain damage.
Some patients in this group have been proceeded to organ harvest with discontinuation of care with no conclusive evidence of permanent and irreversible loss of brain function on the basis of a paltry CT, despite respiratory efforts (breathing spontaneously) and despite physical findings, ie 'bowel sounds' and automic reflexes with tachycardia and hypertension evident (which support normal subcortical functions), which is totally inconsistent with 'whole brain death'.
CAVEAT: GBS patients with a spontaneous breathing pattern may require prolonged ventilation.
Any negligence of the patient's throat secretions may lead to aspiration of vomitus or gastric content and a vicious cycle begins, which if not broken can lead to death.
When life support is discontinued, death results from respiratory paralysis and subsequent asphyxiation. In the strict medico-legal sense it signifies asphyxia, caused by lack of oxygen or obstruction of the breathing passages.
As a safeguard in determining brain death a number of tests need to be carried out every 6 hours and recorded, the physicians performing this determination must not be part of a transplantation team. Glasgow Coma Scale should be cautiously applied as a prognostic measure in patients with metabolic or toxic CNS insults. In some cases, 48 to 72 hours is required to evaluate brain death and a repeat examinations are required to increase the diagnostic yield with observation up to 24 hours is sometime needed. The length of time between serial examinations to declare brain death varies marginally from 6 to 72 hours.
A number of physiologic changes occur in GBS and are the very same physiologic changes seen in brain death: hemodynamic instability (response to respiratory challenges), endocrine abnormalities, hypothermia, coagulopathy, pulmonary dysfunction (with paralysis of breathing muscles), and electrolyte imbalances (related to Na neglince). Endocrine gland dysfunction in GBS is due to lack of tissue response.
The term "hemodynamic instability" is most commonly associated with an abnormal or unstable blood pressure, especially hypotension. Here, hemodynamic instability will be defined more broadly as global or regional perfusion that is not adequate to support normal organ function. This definition recognizes the obligation to insure adequate organ perfusion during the flaccid period.
The majority of patients experience GBS as the frightening illness it is. Patients may be almost paralysed for a while. In very serious cases, the entire body can be paralysed, even including the eye muscles. GBS can, very rarely, present with coma and absent brainstem reflexes. These patients are NOT 'brain dead'; their brains and sense of hearing and smell work perfectly well, and the patient is alert and conscious of what is going on around him or her. But he/she may literally not be able to move a muscle in response.
Some physicians have proposed actively euthanizing comatose patients for their transplantable organs, a suggestion that is particularly disturbing in light of a British study that indicated that up to 41 percent of 'permanently comatose' patients had been "misdiagnosed" and that some were actually awake and aware.
Understanding GBS is to see it for the nightmare that it really is. Put yourself in the position of a GBS patient with near total, or complete paralysis, and with most of your senses blunted, unable to move, speak or even open or move your eyes due to a severely paralyzed motor function - you try relentlessly to free yourself until you become overwhelmed by exertional fatigue or stress, fright and panic that your heart rythm begins to change rapidly and eradically, as evidenced by sinus tachycardia (>90/min) and hypertension with awareness.
GBS is primarily an iatrogenic, or hospital-acquired condition. Sudden and unexpected deaths have occured. Causes of death are most often secondary to the victim's level of care, or more specifically the lack thereof. Legal pitfalls are at issue in terms of liability.
GBS is associated with prolonged length of ICU and hospital stay and requirement for rehabilitation, with significant use of healthcare resources and cost implications, and is a motive for medical murder.
MashCan is warning the public about medical murder and the organ trade in Canada. This website was created in response to compelling evidence that more and more patients are being killed in Canadian hospitals for their body parts. "Hospitals are on constant watch for organs, and are known to provoke fatal outcomes in cases where they are likely to obtain body parts."
Brain death may be described as an esoteric creation of neurologists and neurosurgeons who are seeking to speed up the declaration of death for the purposes of an eye transplant. The general practicing physician does not rely on those esoteric criteria in pronouncing a person dead." He used the questionable "brain death criteria" based on a paltry CT as a pretext to operate and remove the eyes.
A CT scan is useful only in pretty severe cases, such as trauma, and also during the few days after an anoxic (lack of oxygen) brain injury. It’s useful in an emergency-room setting. But if the question is ischemic injury [brain damage caused by lack of blood/oxygen to part of the brain] you want an MRI and PET. For subsequent evaluation of brain injury, the CT is pretty useless unless there has been a massive stroke.
It goes without saying that untreated hyperglycemia can rapidly progress to hyperglycemic hyperosmolar nonketotic syndrome (a metabolic derangement that occurs principally in patients with adult-onset diabetes). Diabetic neuropathy ALSO leads to loss of nerve function. Diabetes is the most common endocrine disorder.
CAVEAT: Hyperglycemia can lower the serum sodium concentration by 1.6 mEq/L for each 100 mg/dl. Hyperglycemia itself is also a risk factor for "soft-tissue infections", ie. abscess.
Canadian standards do not test function of the "entire brain"; does not assess subcortical function of structures such as the hypothalamus-pituitary axis. Many patients diagnosed as brain dead have intact neurohumoral control of hypothalamic-pituitary function, demonstrate normal hypothalamic mediated thermoregulatory control, and have intact autonomic function: they do not have hemodynamic collapse, they have physical findings such as bowel sounds, and are reported to have autonomic reflexes (tachycardia and hypertension) at the time of organ retrieval.
Given that current clinical testing does not assess subcortical brain function, ‘whole brain death’ cannot be conclusively identified at the bedside by using clinical criteria, and certainly not on the basis of a paltry CT.
Brain death is what happens when ventilator support is discontinued. Condition called cerebral hypoxia or cerebral ischemia, is the direct result of oxygen deprivation to the brain cells. If proper balance is not restored or corrected, the heart and lungs may fail and the brain will literally begin to suffocate.
After several minutes of total oxygen deprivation, the brain may not be able to recover any meaningful function. The autonomic system controlling the heart and lungs fails next, leading to the ultimate cause of death, being oxygen deprivation of the brain cells, akin to "asphyxia".
It is never permissible to take any direct action designed to kill the patient. If a doctor deliberately let a patient die who was suffering from a curable treatable illness, the doctor would certainly be to blame for what he had done, just as he would be to blame if he had needlessly killed the patient. Charges against him would then be appropriate. If so, it would be no defense at all for him to insist that he didn't "do anything". He would have done something very serious indeed, for he let his patient die.
To allow or hasten a patient's demise to cover-up medical error or negligence is reprehensible. It is nothing short of murder since such an act or omission carries the intended consequence of the act or omission and therefore the mens rea or criminal intent. Negligence is where the accused ought to have foreseen the consequences of his actions, or inactions.
WARNING: GBS can mimic almost any neurological disease process, including "drain death", effective allowing cover-up of drug induced medical error.It may be possible to sort through these differentials depending on the clinical features described.
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