Guillain Barre Overlap Syndrome
Guillain-Barre syndrome (GBS) is a group of autoimmune syndromes consisting of demyelinating and acute axonal degenerating forms of the disease. Axonal neuropathies have multiple causes. Nerve conduction study helps differentiate the heterogeneous subtypes. GBS is a disorder in which the body's immune system attacks part of the peripheral nervous system.
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Clinical Features of GBS
Ataxia is usually the predominant feature, with a milder element of sensory loss, however the cardinal clinical features of Guillain-Barre syndrome (GBS) are progressive, diffuse muscle weakness. usually accompanied by absent or depressed deep tendon reflexes.
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Presenting symptoms
Presenting symptoms of GBS may include pain (especially back or joint pain), paresis of the extremeties, cranial nerve compromise, ataxia, and associations of different types of symptoms, or overlaping spectrum of unusual presenting symptoms and/or atypical variants of GBS. People with GBS suffer from a wide range of symptoms. Symptoms occur in the context of each patient's unique pattern of focal deficit.
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.
Neurological examination may reveal "no focal deficits". Patients may present with facial weakness mimicking Bell palsy; together with varying degrees of weakness and/or unsteadiness. Patients often appear to be nauseated and in a state of total exhaustion, marked by a haggard appearance. Neurological examination may be otherwise unremarkable.
Mild cases of Guillain-Barre syndrome may present only with ataxia (difficulty in walking and balancing), whereas severe cases may present with difficulty in respiration due to paralysis of the respiratory muscles and cranial nerves. Involvement of facial, oropharyngeal, and ocular muscles results in facial droop, dysphagia and dysarthria; a mournful or expressionless face and drooping eyelids is caused by facial muscle paralysis; difficulty, with alterations in speech patterns or dysarthria is also attributed to muscle paralysis.
Speech may be unintelligible, "slurred" or whispery with GBS, as the various muscles required to form speech are weakened. 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. Severe forms of GBS may result in urinary or fecal incontinence. A history of grossly bloody stools may be observed; fecal leukocytes are usually present.
Cues & clues: Change in pitch range of the voice; Speech difficulties, ie. Slurred speech; Facial weakness, dysphasia or dysarthria; early severe ptosis "drooping eyelid," with or without other signs of oculomotor weakness.
Symptoms of GBS get worse very quickly. The clinical features of GBS can range from asymptomatic to life threatening. It may only take a few hours to reach the most severe symptoms. The disorder can develop over the course of hours or days, or it may take up to 3 to 4 weeks. The consequences of a missed diagnosis and delayed treatment can be catastrophic.
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Flu-like
GBS frequently follows a flu-like illness, or viral syndrome by a week or two. Influenza infection itself can occasionally precipitate the occurrence of Guillain-Barre syndrome, Even the flu jab can cause it.
What to watch for: ataxia and decreased muscle tonus with a preceding flu-like episode absence of fever at onset and associations of different types of symptoms or overlaping spectrum of unusual presenting symptoms and/or atypical variants of GBS.
Signs of autonomic dysfunction are present in 50 percent of patients, including Cardiac dysrhythmias (asystole, bradycardia, sinus tachycardia, and atrial/ventricular tachyarrhythmias), Orthostatic hypotension,Transient or persistent hypertension, Paralytic ileus, Bladder dysfunction, Abnormal sweating.
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Prodromal Malaise
GBS is a prodromal malaise. In medicine, a prodrome is an early symptom(s) indicating the development of a disorder or disease, or that an attack is imminent. For example, low-grade fever, malaise, anorexia (lack of desire to eat), and chills, are all part of the prodrome for the Guillain-Barre 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). A history of grossly bloody stools may be observed; fecal leukocytes are usually present. Respiratory dysfunction may be compromised before signs are clinically obvious.
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Sensory loss
Sensory loss in GBS, 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. This results from dysfunction to position sensing (proprioceptive) nerve inputs. Loss of proprioception causes abnormal placement reactions in the limbs (legs), as well as abnormal limb position at rest. This means that the brain is confused as to the position of limbs - not knowing exactly where your limbs hands and feet are. Some common signs of proprioceptive dysfunction are clumsiness, a tendency to fall, a lack of awareness of body position in space, and unusual body posturing, or posturing. The abnormal posturing may persist during sleep. Sensory ataxia in the Miller Fisher variant can be detected by postural body sway. Loss of proprioception accounts for the ataxia (unsteady gait), postural instability, and/or impaired balance and coordination.
The term employed to indicate ataxia due to loss of proprioception is called Sensory ataxia. Sensory ataxia is sometimes one of the most prominent symptom in idiopathic acute polyradiculoneuritis (Guillain-Barre syndrome) and serological overlap between Miller Fisher syndrome and acute sensory ataxic neuropathy. The overlap accompanied by limb weakness, suggests a transition between GBS and variant MFS.
There may also be concurrent or overlapping limb hypotonia. GBS patients are usually hypotonic or flaccid as well as immobilized. Flaccid (hypotonic) paralysis of gradual onset is usually due to peripheral nerve disease. Flaccid muscles are profoundly weak and soft.
Hypotonia in GBS
The most common symptoms of hypotonia in GBS involve problems with mobility and posture, breathing and speech difficulties, lethargy, ligament and joint laxity, and poor reflexes. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control or muscle strength. It is not the same as muscle weakness, although the two conditions can co-exist in patients with Guillain Barre syndrome.
Hypotonia in Guillain-Barre 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; also notable for a "soft, non-tender abdomen". The abdominal muscles feel 'soft and doughy'. Also a sign of gastroparesis (IMPAIRED STOMACH EMTYING) in clinical diabetes, which can rapidly progress to intestinal obstruction. The most common symptoms of hypotonia in GBS involve problems with mobility and posture, breathing and speech difficulties, lethargy, ligament and joint laxity, and poor reflexes. Some hypotonics may experience constipation, while others have no bowel problems.
A flaccid, or hypotonic, bladder ceases to contract fully, causing urine to dribble out of the body. This type of bladder disorder occurs when the volume of urine is large but the pressure is low.
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Neurogenic bladder
Guillain-Barre Syndrome can impact the muscles that control bladder and intestinal function. Neurogenic bladder can result from neurological conditions such as Guillain Barre syndrome, MS and disorders of peripheral innervation, including autonomic neuropathies resulting from endocrine disturbances such as diabetes mellitus. The primary symptoms of a neurogenic bladder are urinary incontinence, residual urine after voiding, inability to sense the need to void, and urinary tract infection. Sometimes a neurogenic bladder (which is not infected) can mimic many of the symptoms of UTI.
Urinary incontinence may occur early in this disorder as a result of peripheral and autonomic nerve dysfunction. A "motor paralytic bladder" can occur when there is selective involvement of efferents to the bladder or their motor neurons such as in poliomyelitis or Guillain-Barre’ syndrome.
Constipation: The rectum is located near the bladder and shares many of the same nerves. Consequently, megacolon may develop.
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Diffuse Weakness
Diffuse, body-wide form weakness with difficulty ambulating occurs in variant forms of Guillain-Barre syndrome (GBS). It usually occurs in onset acute motor axonal neuropathy (AMAN). A recent history of increasing or diffuse muscle weakness and paralysis may indicate GBS, especially if there was a recent illness. GBS progresses to its fullest extent with diffuse muscular weakness, greater in the proximal muscle groups, followed by early loss of reflexes and parasthesia. Patients described as having Miller-Fisher syndrome often have a neuropathy that overlaps with GBS may also demonstrate generalized weakness. 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.
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Ophthalmoparesis
Increased attention to the eyelid manifestations of the Guillain Barre syndrome has shown a variety of eyelid abnormalities including lid lag and lid retraction. Optic nerve involvement may be a result of either optic neuritis or papilloedema. Ophthalmoparesis is the most frequent ocular sign in Guillain Barre syndrome and third-nerve abnormalities occur in 10 - 17% of patients. T Georgiou
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Immune-Mediated
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 immune mediated neuropathic reaction to contraindicated medications, or both. The pathogenesis of a neuropathic reaction involves an autoimmune reaction to peripheral nerve tissue. 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.
The most serious complications of serum sickness are nerve conditions such as Guillain-Barre syndrome, and peripheral neuritis. Many of the more commonly reported reactions include hypotonia, dysarthria, dysphasia, somnolence, dizziness, paresthesia, nausea, vomiting, and headache, are clearly drug related.
Central nervous system complications of many pharma-agents include aseptic meningitis and Guillain-Barre syndrome. While GBS has been found more freequently than expected in cancer patients, this association is extremely rare. There have been rare cases of GBS caused by chemotherapy, and possible associations with radiation therapy.
GBS is a catastrophic condition which can be triggered by something as innocuous as a cold or stomach upset. Even the flu jab can cause it. 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 an uncommon paralysing illness, caused by autoimmune inflammation of nerves, which most often follows a therapeutic regimen for a "flu-like illness".
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 mistakenly 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. A person with GBS may sometimes feel funny sensations in their skin, or tingling— this is because the nerves that transmit messages about sensation are not working properly. Paralysis results because nerve signals can no longer pass to muscles.
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 tingling, numbness, or paralysis.
Cross-reactions between penicillin and sulfa-drugs are common triggers of drug-induced GBS serum sickness, and fixed drug eruptions. Cipro and Septra DS have been implicated high on the order of major offenders in drug-induced GBS. It is also well documented that Cipro causes drug-induced serum sickness which can rapidly progress to Guillain-Barre 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-Barre syndrome.
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T-cell depression
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. T-cells are usually the first to fall in radiation therapy. Thus lymphocytopenia and incomplete recovery are consistent with immunocompromise in patients with GBS.
T-cell depression in GBS, marked by a drop in the absolute number of lymphocytes is usually associated with iatrogenic causes, most often secondary to drugs, most notably penicillin based medicines, and sulphamides such as Bactrim. It is also well documented that Cipro causes drug-induced serum sickness which can rapidly progress to GBS as one of its most serious complications.
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Dysregulation
The hypothalamus (the part of the brain that works directly with the pituitary gland to produce hormones) is also a "target" for 'post-infectious immune-mediated' disease. GBS is a postinfectious, immune-mediated disease. As such, GBS can impact the hypothalamus which regulates homeostasis via functions of hypocretin affecting regulatory areas for thirst, hunger, body temperature, water balance, blood pressure, and especially sleep and arousal states with links from the nervous system to the endocrine system. In patients with GBS. the hypothalamus produces ADH inappropriately due to hypothalamic dysfunction via damage to neurons in the hypothalamus. The hypothalamus has a direct affect on the pituitary gland. The hypothalamus and the pituitary gland are part of our endocrine system. Adrenal glands work hand-in-hand with the hypothalamus and pituitary gland.
There is strong evidence that narcolepsy is associated with abnormalities of the hypocretin neurotransmitter system.
Epidemiological Features
The most characteristic epidemiological feature of Guillain-Barre Syndrome is the occurrence of an infection and subsequent treatment prior to the onset of illness. Many cases have been linked to recent bacterial of viral infections, vaccinations, or surgeries, including inappropriate and deleterious therapies.
Deleterious effects of a therapeutic or diagnostic regimen causes pathology independent of the condition for which the regimen is advised. Many of the reported cases follow a "flu-like", or gastrointestinal illness with a causal link to certain medications, resulting in drug-induced decreases in the body's ability to recognize and attack invaders. 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. Untreated conditions are also high on the order of possible causes.
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Bickestaff's Variant
A further variant of GBS, 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). Large, irregular hyperintense lesions located mainly in the brainstem, especially in the pons, midbrain and medulla are described in the literature. BBE despite severe initial presentation usually has a good prognosis. MRI plays a critical role in the diagnosis of BBE.
The relationship between the classical and atypical cases of Miller Fisher syndrome, Guillain-Barre syndrome and Bickerstaff's brain stem encephalitis is well documented. There is a clinical continuum between Bickerstaff brainstem encephalitis and Miller Fisher syndrome. with overlapping GBS and Bickerstaff's brainstem encephalitis (BBE).
Bickerstaff's brainstem encephalitis is an immune disorder of unknown aetiology with acute, progressive cranial nerve dysfunction, associated with cerebellar ataxia and coma. Bickerstaff brainstem encephalitis is associated with the presence of anti-GQ1b antibodies. A considerable number of BBE patients have associated axonal Guillain–Barre syndrome, indicative that the two disorders are closely related and form a continuous spectrum.
Bickerstaff reported eight patients who, in addition to acute ophthalmoplegia (diplopia) and ataxia, showed drowsiness, extensor plantar responses or hemisensory loss.
Clinical deterioration in Bickerstaff's brainstem encephalitis is caused by overlapping Guillain-Barre syndrome. There is a clinical continuum between Bickerstaff brainstem encephalitis and Fisher syndrome. It may result in apnoea and a reversible brain death picture.
Epidemiology
Very rare. Mostly reported in adults but cases affecting children have also been reported.
There is a seasonal variation in the occurence of GBS: Mean 40 years of age High freequency in Spring (March to May).
Very often follows preceding illness and an association with certain infections, including cytomegalovirus, Campylobacter jejuni, typhoid fever and Mycoplasma pneumoniae, has been documented. Presentation
Acute diplopia
Ataxia
Pyramidal tract paralysis
Disturbance of consciousness
Headache is common
Progressive, symmetrical ophthalmoplegia, ataxia and either disturbance of consciousness or hyperreflexia
Facial palsy, extensor plantar reflex, pupillary abnormality, nystagmus and bulbar palsy
Differential diagnosis
MRI scan abnormalities; Multiple Sclerosis, Behcet's disease , Lyme Disease, progressive multifocal leukoencephalopathy, sarcoidosis, Whipple's disease, listeria rhombencephalitis, vasculitis due to systemic lupus erythematosus (SLE), and acute disseminated encephalomyelitis all produce similar inflammatory lesions in the brainstem and cerebellum.
Investigations One review of 62 patients found positive serum anti-GQ1b IgG antibody in 66%, and brain abnormality on MRI scan in 30% of patients.
The presence of anti- GQ1b antibodies and an abnormal brain MRI can help to support its diagnosis but absence of anti-GQ1b antibodies and a normal MRI do not exclude the diagnosis, which remains based on clinical criteria and exclusion of other aetiologies.
Associated diseases
A large number of patients have associated Guillain-Barre syndrome, suggesting that the various disorders are closely related.
Miller Fisher: syndrome of ophthalmoplegia, ataxia and absent reflexes.
Management
Prognosis
Although the initial presentation is severe, there is usually a good outcome with complete resolution.
Divisions of the nervous system explained in simple language:
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PART 2
Case PresentationA 41-year-old woman presented to the emergency department in a wheelchair complaining of difficulty ambulating.The patient's family first noticed symptoms of weakness two weeks before admission, first in her right leg and then in both. The weakness was mild and stable until 3 days prior to admission, at which time it began to get steadily worse. At this time, the patient also began noticing numbness in her hands or odd sensations with no energy, dizziness and imbalance. At the time of her presentation to the emergency department, she had difficulty walking.
On physical examination, the patient's blood pressure was 115/70 supine. Her pulse was 79 bpm and regular. She was alert and oriented. Her respiratory rate was 18. Head and neck examination was otherwise unremarkable. The abdomen was soft, non-tender, no masses, and bowel sounds were present. She was afebrile.
Her mental status was normal, but speech was slurred. Inspection of the muscles showed "mild diffuse weakness". The time course of the symptoms correlates with an acute polyneuropathy. Aside from those already noted, the patient had no other neurological symptoms, however, she appeared to be sedated.
The record at A-20 documents a Glucose of 13.2 H mmol/L (the normal range is 4.1 - 7.8): >236 mg/dl. Nerve damage can occur when blood sugars rise over 140 mg/dl (7.8 mmol/l) after meals; especially >100 mg/dl fasting glucose. Symptoms of severe high blood sugar include drowsiness and difficulty waking up. Acute hyperglycemia associated with enhanced neuronal damage following induced brain ischemia can neither be confirmed nor ruled out.. High blood sugar (hyperglycemia) usually comes on slowly, however, hyperglycemia in critically ill patients has been described as a "toxic metabolic milieu" which if left untreated, slowly and insidiously results in catastrophic decline. Further, cerebral edema can also occur unpredictably in this patient group (especially with hypotonic fluids) from overly rapid electrolyte correction.
CAVEAT: Plasma glucose >120 mg/dl in the absence of diabetes = clinical sign of sepsis.
One of the most important remaining conditions to consider is diabetic neuropathy. Several aspects of this case are consistent with diabetic neuropathy. Clinically, diabetic neuropathy has been associated with postural hypotension and constipation is the most common gastrointestinal symptom in diabetic neuropathy. Also, diabetic neuropathy is frequently associated with areflexia in the distribution of the affected nerves. While the diabetic neuropathy accounts nicely for the patients autonomic symptoms and is consistent with uncontrolled hyperglycemia, it cannot account for many of the remaining symptoms.
(Parry, 1993, p.15)
It seems likely that diabetic neuropathy may have contributed to at least some of her symptoms. However, it is unlikely to account for all of this patient's symptoms. Thus, the clinical diagnosis based on this patient's constilation of symptoms and catastrophic decline may best be described as an acute demyelinating polyneuropathy with features of Guillain Barre Syndrome and its variants, BBE and MFS, respectively, against a background of diabetic neuropathy. Miller Fisher Syndrome and Guillain-Barre syndrome are variant forms of acquired demyelinating polyradiculo-neuropathy. Bickerstaff's brain stem encephalitis shares many clinical features but also includes altered consciousness and signs of central nervous system inflammation. Demyelinating neuropathies are commonly inflammatory and treatable.
Acute inflammatory demyelination is a unique disorder simulating brain neoplasm. Acute inflammatory demyelinating lesions present as large masses that mimic brain tumors. Because of demyelination, mass lesions mimic brain tumors on CT or MRI and may be misinterpreted as metastatic cancer of the brain. Abnormal lesions (high-intensity) with clinical symptoms are compatible with typical BBE. These MRI signals may move or regress with the clinical course of the illness (Mond'jar et al., 2002). However, demyelination, as evidenced by slow conduction velocity and conduction block, are reversible features of the disease. Headaches, motor deficits and speach problems are the most common presenting symptoms. 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.
Fisher syndrome, a brainstem encephalitis, also mimics brain death. MFS presents similar to GBS 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. The nerve pathways controlling eye muscles may become affected resulting in total ophthalmoplegia (eye paralysis). There may be no verbal response, no motor response, and no occular response.
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. Blood-brain barrier (BBB) disruption is accompanied by cerebral edema.
Headache in GBS variants
Headache associated with miller fisher syndrome and GBS are unusual but have been reported. Irritated, inflamed or damaged nerves in the brain, spinal cord or body can cause headache with increasing severety, as can ophthalmoplegia associated migrain seen in the Miller Fisher variant of GBS, as the disorder progresses. Alterations of consciousness go with the Bickerstaff's variant: headache type affecting the brainstem. implicated in the maintenance of arousal, but is a worrisome feature of this type of headache called a Bickerstaff's migraine.
Other features of Bickerstaff migraine go with involvement primarily of the brainstem including clumsiness and gait unsteadiness, ie. "pulling to the right". Typical pain is occipital or in the back of the head. Basilar migraine, also called Bickerstaff's syndrome, is characterized by aura that sometimes leads to temporary blindness. The migraine that follows is often accompanied by vomiting. Migraine literature also groups basilar migraine in with hemiplegic migraine and ophthalmoplegic migraine under the heading of "complicated migraines."
There is ophthalmoplegic migraine that implicates the oculomotor (IIIrd) nerve with ptosis and double vision that may or may not involve the pupils or sometimes the VIth or abducent nerve. The pupils of a person's eyes may dilate, or enlarge, in response to stress. Headache associated With Miller Fisher Syndrome may be caused by antibody-mediated effects on the trigeminovascular pain pathway.
Meningitis or meningeal infiltrative disorders usually result in third cranial nerve palsy and 3rd cranial nerve palsy is an exceptionally rare manifestation of GBS, expanding the spectrum of clinical signs and neuraxisinvolvement that may be seen in the condition. Although third-nerve palsy occurs in up tp 17% of cases, most resolve without sequelae.
In women, migraine attacks can also be triggered by hormonal changes during menstruation (periods).
Acute paralysis in GBS
Acute paralysis in Guillain-Barre syndrome (GBS) is related to a Na negligence. It is associated with morbid and iatrogenic events involving IV salt and water, and channel blocking factor in the cerebrospinal fluid.
The neurophysiological abnormalities seen in Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, and multiple sclerosis, traditionally regarded as the result of demyelination may also be explained by sodium channel dysfunction commonly regarded as electrolyte disorders.
A novel Na+ channel blocker may exhibit analgesic effects in some. The assumed mechanism of action to effect analgesia is the acute blocking of sodium channels. The role of analgesic and/or antiepileptic drugs with sodium channel blocking properties are the very same drugs known to exacerbate autonomic dysfunction encountered in Guillain-Barre syndrome (GBS) and multiple sclerosis (MS). Autonomic dysfunction is a frequent and severe complication of Guillain-Barre syndrome, giving rise to the hypothesis that some GBS cases may therefore have a subclinical peripheral neuropathy of osmotic aetiology and that Guillain Barre Syndrome is also an iatrogenic disease.
Fulminant GBS can rapidly progress to a pseudo-coma state resembling acute unconsciousness, but with self-awareness preserved. BBE, Miller-Fisher syndrome (MFS) and Guillain-Barre syndrome (GBS) are similar clinically; BBE and MFS have been postulated to be the variant of GBS. Bickerstaff's brainstem encephalitis (BBE) is characterized by acute onset of ophthalmoplegia, ataxia, disturbance of consciousness, hyperreflexia or Babinski sign (Bickerstaff, 1957; Al-Din et al.,1982).
Early recognition of fulminant GBS and/or its variants is important to prevent inappropriate declaration of brain death or withdrawal of life support in the face of potentially reversible causes.
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Obtundation
Obtundation refers to a reduction in alertness and arousal. A comparable awake conscious state simulating unresponsiveness may also occur in severe cases of peripheral polyneuropathy as a result of total paralysis of limb, bulbar, and ocular musculature. The diffuse polyradiculoneuropathy can make a patient behaviorally unresponsive, although s/he may be perfectly lucid with respiratory support.
Pseudocoma
The locked-in syndrome (LIS) or pseudocoma, describes patients who are awake and conscious but selectively de-efferented, i.e., have no means of producing speech, limb or facial movements. GBS may herald a "locked-in" state of 'outer calm inner panic' due to a severely paralyzed motor function that patients are able to recall vividly and unpleasantly. Transient LIS cases have been reported after Guillain Barre polyradiculoneuropathy (Loebet al., 1984; Bakshi et al., 1997; Ragazzoni et al.,2000) and severe postinfectious polyneuropathy (Carroll and Mastaglia, 1979; ODonnell, 1979). The locked-in state (LIS) involves damage to corticospinal and corticobulbar pathways in the basis pontis. GBS causes bilateral profound damage to these pathways with diffuse compromise to peripheral nerves. Nerve conduction study helps differentiate the heterogeneous subtypes of GBS.. Although patients with GBS in the setting of preserved consciousness may be described as obtunded, these patients may be fully lucid; ambiguities in deciding whether some individual patients are truly unconscious, in a vegitative state, or simply locked-in (implies fully preserved consciousness) cannot be diagnosed at bedside, or on the basis of a paltry CT.
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Variants
Several variants of Guillain-Barre syndrome ( GBS) are recognized and clinically similar states leading to catastrophic decline have been reported to occur with a variety of drugs and biologics. Central nervous system complications of many pharma-agents include aseptic meningitis and GBS.
Acute panautonomic neuropathy is probably the rarest of all the GBS variants. Diffuse sympathetic, parasympathetic nervous systems are involved. Cardiovascular involvement is common (postural hypotension, tachycardia, hypertension, dysrhythmias). The acute panautonomic neuropathies appear to comprise an overlaping spectrum of unusual presenting symptoms and/or atypical variants of GBS with a somatic/autonomic involvement.
Patients usually present a few days to a week after onset of earliest symptoms, looking exhausted and unwell. The typical GBS patient presents with a variety of complaints 2-4 weeks after a relatively benign respiratory or flu-like gastrointestinal illness. Malaise, headache and anorexia or lack of desire to eat are all part of the prodrome for the Guillain-Barre syndrome. Sensory changes are not observed except for infrequent circumoral and peripheral paresthesia (non-painful sensations) from hyperventilation as a patient becomes frightened by onset of paralysis. This patient group often remains afebrile unless they also have acquired a secondary infection. However, they often appear lethargic and have communication difficulties or slurred speach because of bulbar palsies. Marked blood pressure lability with alterations between hypertension and hypotension following paresis suggests an atypical course of GBS.
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While GBS has been found more freequently than expected in cancer patients, this association is extremely rare. There have been rare cases of GBS caused by chemotherapy, and possible associations with radiation therapy. 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. T-cells are usually the first to fall in radiation therapy. Thus lymphocytopenia and incomplete recovery are consistent with immunocompromise in patients with GBS.
Ropper, Wijdicks and Truax, 1991, report that the average age of Onset: Mean 40 years of age; Seasonal: High freequency in Spring (March to May).
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-Barre syndromes can overlap.
MFS is both a peripheral and central nervous system disorder with an immune-mediated pathogenisis which mainly involves the peripheral nervous system with rare involvement of other parts of the central nervous system. All variants have in common absent or diminished tendon reflexes, elevated CSF protein concentrations, and electrodiagnostic abnormalities.
GBS is the commonest peripheral neuropathy causing respiratory failure. It 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, including a variety of primary and secondary disorders. The Guillain-Barre syndrome may present with a wide range of clinical pictures. The symptoms of GBS and its variants can affect each patient differently and with varying intensities, so each patient can have a unique case history. In the initial stages, the patient is likely to have few if any symptoms (Hughes, 1995). Some cases may be so mild that medical attention is never sought, and there are case reports of patients with near total or total paralysis, and some who were only able to move a few fingers and/or wiggle some toes, retaining only a little motion in some fingers or a foot. In very serious cases, the entire body can be paralysed, even including the eye muscles.
Babinski's sign is a prominent finding in Bickerstaff's brainstem encephalitis (BBE), including the Miller-Fisher variant of GBS. In fact, many of these patients are reported to have retained the ability to wiggle their toes or feet up and down and plantar flex. In some cases, the only way the patient could communicate was by wiggling the toes yes or no.
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GBS can be devastating because of its sudden and unexpected onset.
The weakness may progress over hours to days to involve the arms, truncal muscles, cranial nerves, and muscles of respiration. The illness progresses from days to weeks, with the mean time to the nadir of clinical function being 12 days and 98% of patients reaching a nadir by 4 weeks. A plateau phase of persistent, unchanging symptoms then ensues followed days later by gradual symptom improvement, with a slow recovery but in this case no diagnosis was made in a timely manner.
Guillain-Barre syndrome 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). As the weakness progresses upward, the arms and facial muscles also become affected, and fail to work. 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.
_________________________________________________________________________With GBS, speech may be unintelligible, "slurred" or whispery as the various muscles required to form speech are weakened. A recent history of increasing or "diffuse muscle weakness" followed by paralysis suggests a typical presentation of Guillain-Barre syndrome, especially if there was a recent illness, or infection. 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. In frail patients, as respiratory rate decreases, the patient becomes increasingly sedated.
In severe cases of GBS, muscle weakness develops so quickly that muscle atrophy doesn't occur, but hypotonia and areflexia do. Areflexia is noted in nearly all Guillain-Barre Syndrome patients and is due to large diameter muscle spindle afferent axon involvement, Parry 1993. Hypotonia in Guillain-Barre 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'.
GBS can freeze the breathing muscles with assault on muscle function resulting in episodic and paroxysmal disorders with progression. Low oxygen saturation may be present with advanced respiratory muscle involvement. If proper balance is not restored or corrected, the heart and lungs may fail and the brain will literally begin to suffocate.
Serious cardiac rhythm are common and appear frequently in patients with GBS and manifests as inappropriate sinus tachycardia, reduced R-R interval variation, postural hypotension and reactive hypertension. BP fluctuations and arrhythmias can be severe, sometimes resulting in fatal cardiovascular collapse. These events are attributed to autonomic dysfunction. 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 panic flight or fight responses. A panic attack in severe GBS is capable of producing obstruction or congestion of the breathing passages, marked by a congested oral airway. Certainly the inability to breathe properly can be alarming, and many persons will immediately react with anxiety, fear, or panic._________________________________________________________________________
GBS is diagnosed on the basis of characteristic clinical findings, especially neurological unique to that disorder. All these findings, including diabetic neuropathy are mirrored in this patient. Although hyperglycemia is uncommon in GBS, it is possible for the two to coexist.
It is always possible to have two or more conditions or diseases rather than just one. For many diseases, there are usually other diseases that are related to it or associated with it. The first disease is a risk factor for the second. Two conditions may be caused by the same underlying condition (i.e. a third underlying condition): for example, diabetes and hypertension may be related due to underlying metabolic syndrome.
Autoimmune diseases tend to occur together. Some examples of autoimmune diseases include lupus, Type 1 diabetes, multiple sclerosis, Guillain-Barre syndrome, and many other conditions. Autoimmune diseases run the gamut from mild to disabling and potentially life threatening. Nearly all affect women at far greater rates than men. Because you have one autoimmune disease, you may have a problem with your immune system, making you more susceptible to other autoimmune diseases. Some patients have multiple autoimmune disorders with symptoms and diagnostic criteria that can and will invariably overlap. In fact, both GBS and diabetes (especially hyperglycemia) share a commonality with 'peripheral neuropathy', infection, coagulopathy, and SIADH, observed in each of these disorders, suggesting a possible shared mechanism, or similar underlying pathological mechanisms. For the same reason, GBS peripheral neuropathy may overlap with other related disorders, including diabetic neuropathy.
Hyperglycemia is said to be common in brain death. One might well argue that most sugar diabetics with hyperglycemia are very much alive. In many patients with high glucose, this is simply high blood sugar, systemic hyperglycemia. It should also be borne in mind that certain medications such as morphine and phenothiazine derivatives actually contribute to the occurance of hyperglycemia. In fact, both have been reported to trigger diabetes in patients with no previous history of diabetes.It is tempting to establish a 'cause and effect' relationship between diabetic neuropathy and GBS, to the peripheral nervous system. For the record, an association of acute motor neuropathy and diabetes mellitus, rather than a chance occurence of the two conditions is reported in the literature. Alternatively, it may also be argued that diabetes, especially hyperglycemia, is common and that the association with Guillain-Barre syndrome is coincidental.
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pseudo-coma-like
GBS with loss of all brainstem reflexes (blink, gag, pupillary reaction to light) and complete flaccid quadriparesis, mimicking cerebral death has been widely reported in the literature. If the injury to the peripheral nerves, including respiratory nerves, is accompanied by facial nerve paralysis, the clinical picture resembles the neurological condition detected in brainstem death. 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".Glasgow Coma Scale
A-26 of the medical record documents the patient's motor responses with a Glasgow Coma Scale (GCS) total score of 3 (No response). The GCS is a numerical classification scale ranging from a score of 3 (deepest coma) to 15 (awake and oriented), combining three sub-scales based on eye opening, verbal response, and motor response to pain.
Gasping for breath - sleep apnea: GBS can freeze the breathing muscles with assault on muscle function resulting in episodic and paroxysmal disorders with progression. Snoring and sleep apnea are part of the same problem. Apnea may occur when a disease that affects neurotransmission to the ventilatory muscles is present. Diseases such as GBS block neurotransmission of the nervous system and may lead to apnea. She was breathing spontaneously, meaning respiratory centres of her brain stem were not damaged.
All this is due to lack of diagnostic thoroughness and complete absence of urgent therapy. This declaration consequently represents a death sentence in itself, announced and put into action after a ridiculously short observation period of a meagre few hours, sending the patient at the mercy of the eye explant procedure. The explant is performed on a patient that reacts to the operatory trauma with evidence of tachycardia and hypertension. For the record, tachycardia and hypertension are an indication of awareness and/or pain, showing a clear response to surgical incision at the time of eye removal. From the facts of this case it seems clear that Arlene Berry, as a human being was deprived of all of her the cardio-respiratory and cerebral functions in order to cover-up medical wrongdoing.The declaration of brain death conceals any malpractice and by its means, the neurosurgeons, the medical examiner or other health vare providers can literally get away with murder. Attempts to expedite organ procurement for transplantation by hastening death are subject to criminal prosecution. Wrongful brain death declaration denies patients and families the right to optimal medical care and exacerbates public distrust in the medical profession.
There are a number of potentially reversible causes of a lower GCS score. Although the GCS is used extensively in predicting outcomes of traumatic and anoxic coma, it is pretty much useless in a sedated patient on a ventilator. Neither is it useful in patients with toxic/metabolic conditions such as diabetes, or a locked-in or Guillain Barre patient who is paralyzed and is unable to speak or respond to pain and who may also have a Glasgow Coma Scale of 3, which may mimic or overestimate depth of coma altogether. In patients with GBS, GCS may improve over days or weeks, but only if supportive care is provided. GBS patients frequently require a great deal of psychological support, given the extremely disabling and frightening aspects of the condition and its sequelae. Undertaking a multidisciplinary approach to GBS patients is an important aspect of overall ICU managemen.
Laboratory abnormalities have included hyponatremia, including an initial CSF neutrophilic pleocytosis, marked by an elevated neutrophil count. Normal CSF protein level does not rule out GBS because the CSF protein level remains normal in 10% of patients and because any rise in the CSF protein level may not be observed until 1-2 weeks after the onset of weakness. Electrodiagnostic studies may show reduced motor amplitudes with normal conduction velocities with active denervation and reduced sensory amplitudes have also been seen.
When clinical or radiological abnormalities are found, the condition may be referred to as Bickerstaff's brainstem encephalopathy (BBE). Encephalopathy with peripheral neuropathy may falsely mimic brainstem death.
OverviewGuillain-Barre Syndrome is a frightening and disabling disease which strikes suddenly, sometimes with devastating effect. Symptoms typically progress over a period of a few days and are usually at their worst two weeks after onset. Symptoms of Guillain-Barre get worse very quickly. It may take only a few hours to reach the most severe symptoms. Patients are paralyzed by the illness, but mentally alert and fearful.
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 actively euthanize comatose patients for their transplantable organs, an ongoing practice that is particularly disturbing in light of a British study that indicated that up to 41 percent of seemingly 'permanently comatose' patients had been "misdiagnosed" and that some were actually awake and aware.
Put yourself in the position of a GBS patient with near total, or complete paralysis, 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. Understanding GBS is to see it for the nightmare that it really is. What it is like to be conscious but paralyzed and voiceless, relates to the terrifying situation of an intact awareness in a sensitive human being, experiencing frustration, fright, stress and anguish, locked in an immobile body, totally paralysed and heartwrenchingly helpless.GBS is usually associated with prolonged length of ICU and hospital stay and requirement for rehabilitation, with significant use of healthcare resources and cost implications is of itself sufficient motive for medical homicide.
Case in point
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way 35% gbs have liver anzime alveted
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