Dr. Barry A. McLellan
Regional Supervising Coroner
Greater Toronto Area (GTA)-East
28 Grenville Street
Toronto, ON
M7A 2G9
RE: Arlene BERRY
Date of Death: May 24, 2000
Your File: 8588/2000
Dear Dr. McLellan
This document is produced persuant to section 15(4) of the Coroners Act,R.S.O. 1990, C.37, on the basis that it is to be used for the sole purpose of aCoroners investigation, and not for any litigation or other proceedings unrelated to the Coroners investigation. Moreover, the opinions expressed herein by the author do not necessarily take into account all of the facts and circumstances surrounding the death. The final conclusions of the Coroners investigation may differ significantly from the opinions expressed herein.
I have reviewed the documents and the images that you have provided me regarding the medical history of Arlene Berry who died on the 24th of May, 2000.
As you are aware, a diagnosis of adenocarcinoma of the lung was made in December, 1999. With respect to neurological function, she remained well until about one week prior to her admission on the 23rd of May, 2000 to the Kirkland and District Hospital. Over that week she had increasingly difficulty walking and tended to fall toward the right side. She developed headaches that became increasingly severe and immediately prior to her hospital admission were associated with nausea, vomiting and drowsiness.
The emergency record from the hospital, dated the 22nd of May, 2000, documents a history of hematuria for three days and a prescription for treatment for urinary tract infection consisting of Bactrim. The physician who saw her (whose signature is illegible) made adiagnosis of urinary tract infection but considered her past medical history, noting that she had had a left lung resection for carcinoma and that her prior head CT showed no metastasis. He notes, in addition, that she was haggard in appearance. What I take to be nursing notes, document that she was pale looking and lethargic.
From this record it seems clear they recognized that she was sick, but on the basis of the clinical findings at that time, they elected not to admit her to hospital. In my opinion, from the record there was no indication that she was about to suffer a catastrophic decline.
You have provided me with a copy of the prior head CT that was done on the 16th of March, 2000. The scan was done with iodionated contrast material which makes tumors more visible. In the right occipital region there is a spot that measures less than 1 cm in diameter that is consistent in appearance with either a small hemorrhage or perhaps a small metastatic tumor. The brain is not significantly distorted and the lesion would have been asymptomatic.
She returned to the emergency department on the 23rd of May, 2000. With the same complaints. At the time of admission she was conscious. The triage notes makes reference to severe stomach pain, vomiting, hematuria and headache. The time of this assessment is documented at 1705 hrs. The admission orders include a request for a CT scan to be done in Timmins which I assume would have been done in 24 hours.
Dr. Jordans discharge note documents a rapid deterioration that by 0245 hrs had resulted in complete cessation of motor response, verbal response and occular response, that is, Arlene Berry had a Glasgow Coma Scale of 3. He documents also that her pupils were midsize and fixed, a sign of brainstem malfunction. She was still breathing spontaneously.
She was then transferred with ventilatory support to Sudbury under the care of Dr. Adegbite where a CT scan was done. It shows several large metastic tumors with massive oedema of the right cerebral hemisphere, a 1 cm shift of the midline structure from right to left and evidence of extreme intracranial hypertension (compression of the third ventricle, obliteration of the ambient cystern and decreased attenuation through much of both cerebral hemispheres suggesting no cerebral perfusion). She was declared brain dead.
It is clear although she remained relatively asymptomatic until the last week or two of her life, Arlene Berry had a particularily aggressive tumor with rapid evolution of several brain metastasis. The largest measures nearly 3 cms in diameter and I can count a total of four distinct tumors. There may, in fact, be more but with the impaired cerebral perfusion due to the high intracranial pressure they are not well opacified.
Had she been started on decadron she might have enjoyed respite from her headache and might have lived a few weeks longer, but with multiple metastatic tumors , she would have been inoperable and, have been pallative. Whole brain radiotherapy would have extended her life a very few months.
In my opinion, the physicians who looked after Arlene Berry met a reasonable standard of care."
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in which dissemination with CNS involvement may lead to brain abscess formation.
Nosocomial infections often occur with antibiotic-resistant strains of Pseudomonas. Can lead to more serious kidney infection (pyelonephritis) if untreated - can be asymptomatic in children and elderly
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SEE TABLE http://www.chclibrary.org/micromed/00054910.html
Infection typically causes flu-like symptoms, followed by an asymptomatic period of months or years during which the patient can transmit the disease.
Most infections are asymptomatic, so disease can be spread by carriers who do not even know they are infected.
The most serious UTI is infection of the kidney (pyelonephritis), since it cvan cause lasting kidney damage. Infection of the urethra (urethritis) and bladder (cystitis) can lead to pyelonephritis (by the ascending route).
http://ca.geocities.com/dynamic_resources2004/FINDLAST.HTM
http://ca.geocities.com/dynamic_resources2004/BrainRegions.html
an infection of the brain is very rare. Yet all of the evidence points to an infectious disease.
http://www.tutorgig.com/ed/third_ventricle
http://www.tutorgig.com/ed/fourth_ventricle
Sudden unexplained death in adults caused by intracranial pathology
http://ca.geocities.com/dynamic_resources2004/Ataxia.html
Multifocal neurologic symptoms suggest neoplas-tic meningitis
http://www.meverett.com/index/abscess.htm/findall2.htm
"Massive haemorrhage into brain substance is characterised clinically by an abrupt onset and rapid evolution"
The most common causes of death in these circumstances are associated with epilepsy, intracranial haemorrhage, either natural or after trauma, and acute bacterial meningitis
there are examples in adults, principal among which are sudden unexplained deaths caused by either acute bacterial meningitis or in association with a large cerebral abscess. Invariably, acute bacterial meningitis is secondary to a bacteraemia in adulthood,
intracranial haemorrhage, either natural or after trauma, purulent meningitis or an abscess
"Massive haemorrhage into brain substance is characterised clinically by an abrupt onset and rapid evolution"
Although intracranial infection occurs most frequently in children, there are examples in adults, principal among which are sudden unexplained deaths caused by either acute bacterial meningitis or in association with a large cerebral abscess. Invariably, acute bacterial meningitis is secondary to a bacteraemia in adulthood, and is most commonly caused by pneumococci and meningococci
an abscess acts as an intracranial expanding lesion. Additional complications are rupture of the abscess into the ventricular system to produce an acute purulent ventriculitis, or rupture into the subarachnoid space to produce an acute purulent meningitis.
any process, such as meningitis or subarachnoid haemorrhage, which results in obliteration of the subarachnoid space (particularly at the level of the tentorial opening) will obstruct the free flow of cerebrospinal fluid. It follows that hydrocephalus will develop rapidly from any lesion in the posterior fossa.
an abscess acts as an intracranial expanding lesion
In cases of subarachnoid haemorrhage, it is likely that the sudden enveloping of the brain stem by blood from a ruptured saccular aneurysm induces an autonomic discharge, causing dysrhythmia or cardiac arrest, severe ischaemia of the brain stem by the induction of intense vasospasm, or a rapid rise in intracranial pressure and a pronounced reduction in the cerebral perfusion pressure.
The most common mechanism of death is raised intracranial pressure as a result of an intracranial expanding (space occupying) lesion, as in intracerebral, extradural, and subdural haematoma, tumour, or abscess. If the haemorrhage is massive, there is a rapid rise in intracranial pressure, the cerebral circulation ceases, and death may ensue. Under these circumstances, the conventional features of shift, distortion, internal herniation, and secondary haemorrhage in the brain stem may either be incompletely formed or absent.
A common association with an infratentorial expanding lesion is the increase in the size of the third and lateral ventricles—hydrocephalus
any process, such as meningitis or subarachnoid haemorrhage, which results in obliteration of the subarachnoid space (particularly at the level of the tentorial opening) will obstruct the free flow of cerebrospinal fluid. It follows that hydrocephalus will develop rapidly from any lesion in the posterior fossa. = Sudden unexplained death in adults caused by intracranial pathology
In cases of subarachnoid haemorrhage, it is likely that the sudden enveloping of the brain stem by blood from a ruptured saccular aneurysm induces an autonomic discharge, causing dysrhythmia or cardiac arrest, severe ischaemia of the brain stem by the induction of intense vasospasm, or a rapid rise in intracranial pressure and a pronounced reduction in the cerebral perfusion pressure.= http://jcp.bmjjournals.com/cgi/content/full/55/1/44#SEC5
See Raised intracranial pressure
A common association with an infratentorial expanding lesion is the increase in the size of the third and lateral ventricles—hydrocephalus
Pathophysiology
http://www.indianpediatrics.net/feb2000/personal.htm
Two clinical syndromes after subependymal hemorrhage and intraventricular hemorrhage have been described. The catastrophic syn-drome has a sudden onset and a rapid evolution to coma. Respiratory abnormalities, extensor posturing, seizures, and abnormalities in brain-stem reflexes are present. Severe derangements of metabolic homeostasis occur and mortality is high(32). The saltatory syndrome manifests with an altered level of consciousness, decreased spontaneous movements, lessened responsiveness to external stimuli, and oculo-motor abnormalities. These signs evolve slowly, and a period of stabilization followed by a second episode of deterioration often occurs. Mortality is lower than with the catastrophic syndrome The two primary pathophysiologic features of cerebrovascular disease are interruption of blood flow to part of the brain or rupture of blood vessels with bleeding into the cerebral parenchyma.
Rapid evolution of illness or patient return within 24-48 hr suggests a severe illness. Rapid evolution of illness or second patient visit in less than 24 hr = http://merck.micromedex.com/bpm/bpmtables_print.asp?article_id=BPM01ID16
rapid evolution of the thrombus and coma, involvement of deep veins and cerebellar veins and septic thrombi.
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 CSF, bacteria multiply rapidly due to the absence of local defenses where they further degrade the blood-brain barrier and exacerbate tissue damage
Brain injury caused by meningitis-related inflammation, edema, reduced blood flow (ischemia), or endogenous toxins can lead to many long-term neurologic sequelae, including deafness, mental retardation, motor dysfunction, and (secondary) epilepsy. Although ABM is usually caused by Streptococcus pneumoniae, Neisseria meningitidis, Listeria monocytogenes, Haemophilus influenzae, or group B streptococcus, almost any organism that can enter the brain may cause meningitis.= http://merck.micromedex.com/index.asp?page=bpm_viewall&article_id=BPM01ID16&show_banner=no
http://www.infection.bham.ac.uk/Teaching/pathogenesis.ppt.
the involvement of cardiac muscle supports a toxic etiology. It is important that this serious adverse reaction of propofol be recognized as discontinuation of the drug can lead to rapid recovery from cardiac and renal dysfunction.
Staphylococcus aureus pneumonia is a common presentation.
CT scan revealed a 1cm mass in the left occipital region
Subsequently, contrast CT of the brain revealed mass occupying lesions in both the cerebellar hemispheres with a 2cm lesion
A 41-year-old female outpatient was admitted to hospital with progressive headache, dizziness, and a low-grade fever of 2 weeks' duration.
after the diameter of the abscess becomes less than 2 to 3 cm and does not increase anymore on serial CT, medical treatment alone can be anticipated to give satisfactory results = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10786097&dopt=Abstract
On nonenhanced CT, Toxoplasma encephalitis appears as areas of isointense or hypodense mass effect. The basal ganglia and the corticomedullary junction are most commonly affected. Contrast-enhanced CT demonstrates a ring or nodular enhancement pattern with lesions of 1-3 cm in diameter. The enhancement is greatest within the intermediate zone where inflammation is the greatest. = http://www.emedicine.com/radio/topic91.htm
Often, aspiration alone can treat significant mass effect and prevent rupture of the abscess into the ventricular system. Ventricular rupture of a bacterial brain abscess is often fatal. = http://www.neurosurgeon.org/education/medStudCur/curriculum.asp?inPage=b2
Small abscesses (2.5 to 3 cm) are more likely than large ones to respond
CT-guided stereotactic aspiration of multiple brain abscesses is known to have a low morbidity and mortality.
http://www.egms.de/en/meetings/dgnc2004/04dgnc0424.shtml
http://www.medfamily.org/diagnosis/B/diagnosis-terms-Brain_abscess.phtml
Brain abscess is considered a rare complication ofmeningitis
Microglial activation is a hallmark of brain abscess [4,5,9]. They respond robustly to both S. aureus and PGN with significant proinflammatory mediator expression, and many of these same mediators are persistently elevated in brain abscess. Drawing on this relationship, we have proposed that chronic microglial activation may contribute, in part, to the excessive tissue damage characteristic of brain abscess. Therefore, attenuating chronic microglial activation subsequent to effective bacterial elimination in the brain may result in attenuation of the structural and functional damage associated with brain abscess. = http://www.fleshandbones.com/readingroom/pdf/463.pdf
Adenocarcinoma is a carcinoma that begins in cells that line internal organs (glandular epithelium tissue), and has gland-like properties. Adenocarcinoma -a form of Non-Small-Cell Lung Cancer -is one of the most common lung cancer in women and nonsmokers. = http://www.mesothelioma-asbestosis.info/Lung-Diseases/adenocarcinoma
Adenocarcinoma. This cancer usually begins in the mucous-producing cells of the lung. It's the most common type of lung cancer in women and people who have never smoked. = http://www.caringmedical.com/symptoms/condition.asp?condition_id=941
adenocarcinoma and large cell carcinoma also are related to smoking.
People with adenocarcinoma have a more favorable outlook
A HREF=http://www-medlib.med.utah.edu/WebPath/LUNGHTML/LUNGIDX.html>Pulmonary Pathology Index
Viral pneumonias generally manifest as interstitial inflammatory processes, while fungal and mycobacterial infections are granulomatous. = http://edcenter.med.cornell.edu/CUMC_PathNotes/Respiratory/Respiratory.html
Trauma is another mode of infection by direct extension.
SEARCH: infectious granulomas of the lung).
Epidermoid and adenocarcinoma have about the same 5-year survival probability. It is worse for large cell carcinoma, and oat cell carcinoma has almost no 5-year survival probability with a mean lifespan on the order of months from the time of diagnosis. Overall 8% of lung cancer cases live past 5 years. = http://edcenter.med.cornell.edu/CUMC_PathNotes/Respiratory/Respiratory.html
In patients with brain abscess, subdural empyema, septic emboli, and ventriculitis, these lesions appeared hyperintense on DW MR images, whereas in patients with tumor, the lesion was visualized as a hypointense area.
Patients present with symptoms resulting from the mass effect of the abscess, which often mimic those of a brain tumor.
Confusing a brain abscess with a tumor can have catastrophic consequences with the untimely administration of high-dose steroid agents, rupture of the abscess capsule, or development of cerebritis
Pus has been shown to produce hyperintense signals on DW imaging and to be associated with reduced ADC values, compared with the isointense or hypointense signals and increased ADC values of neoplastic diseases.
These two cuts from his CT scan series show multiple 2-3 cm diameter loculated cystic lesions consistent with multiple abscesses (dark areas with rims of enhancement). There is distention of the posterior fossa with a midline shift toward the right.**
**A brain abscess usually appears as a hypodense center with a surrounding ring which can be contrast-enhanced. Other patterns include nodular enhancement, and areas of low attenuation without enhancement.
A 69-year-old man developed abdominal pain, fever, shaking chills and acute hemiplegia. Computed tomography (CT) scanning demonstrated a hematoma within a thalamic space-occupying lesion having the radiological characteristics of a malignant glioma. Low-grade fever and leukocytosis persisted and follow-up CT scanning showed ring enhancement of the thalamic lesion and ependymitis suggesting a cerebral abscess. Stereotactic aspiration achieved drainage of the abscess and relief of mass effect and provided pus from which a causative organism was identified and treated with appropriate antibiotics = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3329841
a poorly defined pattern of mass effect and low attenuation
Orbital cellulitis may progress to intracranial abscess, as the infection spreads, by causing venous thrombosis and sepsis
Brain abscess. Axial fluid-attenuated
Caption: Picture 29. Brain abscess. Axial T1-weighted gadolinium-enhanced MRI in a patient with multicentric brain lymphoma. Note the moderate mass effect on the left, with multiple areas of enhancement in both cerebral hemispheres (black arrows). This pattern is unlike the more geographic enhancement of a typical cerebral abscess *** = http://www.emedicine.com/radio/topic91.htm
***Symptoms of brain abscess include an altered mental state, headache, fever, seizure, vomiting, unilateral weakness or hemiparesis, and cranial nerve signs.
Neurologic An altered level of consciousness, reflected in a reduction in the Glasgow Coma Score, is the most readily recognizable manifestation of the neurologic dysfunction of MODS. Its causes are multiple, including the iatrogenic effects of sedatives and analgesics, metabolic alterations, subclinical cerebral edema and reduced cerebral perfusion pressure, and, perhaps, micro-abscesses in the brain. =http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=surg.section.5366
Under increased intracranial pressure, the brain expands into the cerebrospinal fluid space, reducing the size of ventricles and subarachnoid space. The cerebrospinal fluid pressure is raised.
Several disease processes may cause disruption of the blood-brain barrier and/or interfere with the brain's supply of oxygen or glucose directly or indirectly, leading to a major and substantial rise in intracranial pressure that exceeds first venous and then arterial perfusion pressure with resulting loss of perfusion of the brain. Once cerebral flow ceases, the nerve cells and the capillary bed are damaged irreversibly.
http://www.pathology.ubc.ca/path425/PrincipleofPathophysiology/Hemostasis/BloodBrainBarrierDrKZis.doc.
http://www.google.ca/search?q=cache:T290DTpCPeQJ:www.pathology.ubc.ca/path425/PrincipleofPathophysiology/Hemostasis/BloodBrainBarrierDrKZis.doc+abscesses+%22loss+of+perfusion%22&hl=en = THE BLOOD-BRAIN BARRIER
***The wall of a well-defined late abscess consists of an inner inflammatory layer, a middle collagenous layer, and an outer gliotic layer. The late capsule stage may last for months = THE BLOOD-BRAIN BARRIER - PATHOLOGY 425
She was under the impression it was a Yeast Infection - the spread of the fungi through the blood stream may cause micro-abscesses in multiple organs. The micro-abscesses in the brain may develop meningitis.
compare: http://www.emedicine.com/med/topic264.htm
Lung and airway infections may result in abscesses also in the lung. Endocarditis and pericarditis are serious just as meningitis and brain abscesses.
Entamoeba histolytica (Amebiasis) These trophozoites most often attack the colon proximally, but may be seen anywhere along the colon and rectum. Histologically, the trophozoites are found in the surface mucous overlying areas of inflammation. Typically they contain contain ingested RBC's. The amoebae resemble histiocytes with a single nucleus and stain PAS + In addition, this organism produces characteristic flask-shaped ulcers in the colonic wall.
Clinically, the symptoms can range from mild to severe dysentery.
Liver, lung, or brain abscesses can occur. = http://edcenter.med.cornell.edu/CUMC_PathNotes/Gastrointestinal/Gastrointestinal.html
inflammation results in edema which lowers perfusion of the brain followed by metabolic acidosis = http://www.medizin.fu-berlin.de/infekt/PDF/CARDS.PDF
Nocardia It is a fungus like (similar to actinomycosis). gram +ve aerobe. Like fungi, from a primary pulmonary site dissemination occurs with 50% involvement of CNS. Single or multiple abscesses which may rupture causing purulent meningitis. CSF finding are non specific and culture is difficult. It is penicillin resistant = http://www.thamburaj.com/Fungus.htm
Central Nervous System Infections: Synonyms and Source Vocabularies
http://www.med.sc.edu:85/2003-infectpdf/03-11CNS.pdf
pockets of infection in the brain (brain abscesses
http://www.surrey.ac.uk/SBMS/ACADEMICS_homepage/mcfadden_johnjoe/pdfs/SBMS212_bacteria_systemic.pdf
As DIC progresses, the patient may experience a fall in blood pressure, ... Thrombosis (abnormal clotting of the blood). ...
A full blood examination is also usually done. Increased platelet count (blood cells involved in clotting) and high erythrocyte sedimentation rate (ESR), which indicates tissue inflammation, help to confirm the diagnosis.
http://pediaindia.net/archive/sickle.shtml
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As regards the association between antipsychotic drugs and sudden death, "all produce side-effects. The principal side-effects include extrapyramidal symptoms (parkinsonism, akathisia, dystonia, and dardive dyskinesia), hypotension, interference with the temperature regulating system, the so called neuroleptic malignant syndrome, and a number of idiosyncratic effects of the cardiac system." Compare: Cardiac effects of antipsychotic drugs.
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