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 ambulating.
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 patient’s autonomic symptoms and is consistent with uncontrolled hyperglycemia, it cannot account for many of the remaining symptoms. Autonomic dysfunction is also a well recognized manifestation of Guillain-Barre with unusual autonomic dysfunction at its onset, consisting of constipation and hypertension, followed by adynamic ileus, endocrine abnormalities and flaccid paraparesis with areflexia. GBS frequently follows a flu-like illness, or viral syndrome by a week or two. 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. Sinus tachycardia,(>90/min), is seen in over 35% of patients with Guillain-Barré Syndrome, and over 30% suffer from hypertension (Parry, 1993). 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 consequences of a missed diagnosis and delayed treatment can be catastrophic.
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-Barré 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 (Mondéjar 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.
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-Barré 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). Alterations of consciousness go with this headache type affecting the brainstem implicated in the maintenance of arousal, but is a worrisome feature of this type of headache. Typical pain is occipital or in the back of the head. 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.
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 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 Barré polyradiculoneuropathy (Loebet al., 1984; Bakshi et al., 1997; Ragazzoni et al.,2000) and severe postinfectious polyneuropathy (Carroll and Mastaglia, 1979; O’Donnell, 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.
Several variants of Guillain-Barré 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.
Presenting symptoms of GBS include ‘flu-like’ symptoms, absence of fever at onset, 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. 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.
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.
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-Barré syndromes can overlap. 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.
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-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’.
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-Barré 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.
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. 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.
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.
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 his brain stem were not damaged.
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 management.
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 medical attendant 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.
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