Toxic and Metabolic Disorders of the Nervous System
Standard Medical Examiner autopsy toxicology tests.
Lead lines in bone
Abdominal pain; headache; anorexia
Acute lead intoxication brain edema
Did lead poisoning make Beethoven deaf?
the Heiligenstadt Testament 1802
You my brothers Carl and Johann as soon as I am dead if Dr. Schmid is still alive ask him in my name to describe my malady and attach this document to his account of my illness, so at least as much as is possible the world may be Ludwig van Beethoven, 1770-1827 reconciled to me after my death.”
Mercury Toxicity The Mad Hatter
Mercury poisoning damages granule cells
Mercury poisoning damages granule cells
Augu st, 20 13
Emissions from the coal-burning power plants release the mercury into the atmosphere, which can travel thousands of miles before coming back to the Earth or the ocean.
Billions of tons of coal being burned in Asia – especially India and China – have sent all the mercury over the Pacific Ocean. That is where it gets into the ocean’s food chain. “The microorganisms – the bacteria — in the sea convert this metallic mercury, which is not terribly hazardous, into another form of mercury called methyl mercury, which is very hazardous,” said Dr. Philip Landrigan, Dean for Global Health at Mount Sinai Medical Center.
What about mercury in vaccines?
December 17, 2012
The American Academy of Pediatrics has endorsed the World Health Organization's stance that thimerosal -- a mercurybased preservative -- should be left in vaccines and should not be subject to a ban contained in a draft treaty from the United Nations Environment Program (UNEP).
The Lanc et, Feb 28 ,
What about the vaccines themselves? Do they cause autism?
1998
The Lanc et, Feb 28 ,
1998
“In most cases, onset of symptoms was after measles, mumps, and rubella immunisation. Further investigations are needed to examine this syndrome and its possible relation to this vaccine.”
So…Do the vaccines cause autism?
No, they don’t
In Yokohama, Japan, MMR vaccine was removed, and the incidence of autism continued to rise.
Lancet, Feb .
6, 2010
In particular, the claims in the original paper that children were “consecutively referred” and that investigations were “approved” by the local ethics committee have been proven to be false. Therefore we fully retract this paper from the published record.
Yup, Fraud • “…not one of the 12 cases reported in the 1998 Lancet paper was free of misrepresentation or undisclosed alteration, and that in no single case could the medical records be fully reconciled with the descriptions, diagnoses, or histories published in the journal.” • “Who perpetrated this fraud? There is no doubt that it was Wakefield. Is it possible that he was wrong, but not dishonest: that he was so incompetent that he was unable to fairly describe the project, or to report even one of the 12 children’s cases accurately? No. A great deal of thought and effort must have gone into drafting the paper to achieve the results he wanted: the discrepancies all led in one direction; misreporting was gross.” BMJ Editorial, January 5, 2011
Yup, misreporting was gross • 7 of the 11 biopsies called abnormal in the report were read as normal during the children’s hospitalization. • 5 of the 12 children in the study had been diagnosed with developmental abnormalities prior to receiving MMR vaccine.
• “Furthermore, Wakefield has been given ample opportunity either to replicate the paper’s findings, or to say he was mistaken. He has declined to do either. He refused to join 10 of his coauthors in retracting the paper’s interpretation in 2004, and has repeatedly denied doing anything wrong at all. Instead, although now disgraced and stripped of his clinical and academic credentials, he continues to push his views.” • “But perhaps as important as the scare’s effect on infectious disease is the energy, emotion, and money that have been diverted away from efforts to understand the real causes of autism and how to help children and families who live with it.” BMJ Editorial, January 5, 2011
And yet…
Arsenic – white matter petechiae (circle) are typical. This specimen also has an area of cortical infarction (arrow)
Manganese Toxicity
Hyperintensities in striatum, globus pallidus, substantia nigra. Patients have extrapyramidal symptoms.
Carbon Monoxide - Basal ganglia lesions are typical, especially the globus pallidus bilaterally
Subacute Combined Degeneration: Vitamin B12 Deficiency
Disorders due to alcohol
Wernicke-Korsakoff Syndrome
Wernicke – •1881- paralysis of eye movements, ataxia, mental confusion •found punctate hemorrhages in gray matter around 3rd and 4th ventricles Korsakoff – •1887-91 – disturbance of memory in long-term alcoholism •gaps in memory are filled by “confabulaton”
Two cases of Wernicke-Korsakoff Syndrome
Wernicke-Korsakoff Syndrome
Wernicke-Korsakoff Syndrome
Petechiae and Iron Deposition in Mammilary Bodies
Peri-Aqueductal Gray Matter
Floor of
4th Ventricle
Cortical involvement in Wernicke’s
Age at Onset of Symptoms in Wernicke-Korsakoff Syndrome Decade 20-29 30-39 40-49 50-59 60-69 70-79
Men 3 12 44 53 38 10
# of cases Women 11 22 25 18 14 0
Leigh’s Encephalopathy
Many mutations – automosomal, X-linked, or mitochondrial, with lesions and symptoms that resemble Wernicke’s. Notice how similar the lesions are.
Central Pontine Myelinolysis
Central Pontine Myelinolysis
Central Pontine Myelinolysis
Alcoholic Cerebellar Degeneration Anterior Vermis
What would the symptoms be?
Marchiafava-Bignami Disease First described in 1903 by two Italian Pathologists 3 men who died following seizures and coma after drinking red wine Middle 2/3 of the corpus callosum was “necrotic”
A 75 year old man was unable to name objects placed in his left hand (tactile anomia), but was able to name them when placed in his right hand.
What abnormality do you see?
Marchiafava-Bignami Disease ?
Fetal Alcohol Syndrome • Small head • Small palpebral fissure • Indented bridge of nose • Smooth area between nose and mouth • Limb and joint abnormalities • Coordination, learning and behavior problems
Fetal Alcohol Syndrome • May be due to acetaldehyde crossing the placenta • Most cases seen in chronic alcoholics • “Safe” amount of alcohol ingestion during pregnancy not established • Microcephaly; cerebellar dysplasia • Effects may be combined with other maternal drug use
Purkinje cells
Normal
Fetal exposure to alcohol
Alcohol and Dementia • Monthly intake of beer associated with significantly higher risk of dementia (all types), compared with non-beer drinkers. • Monthly or weekly intake of wine associated with a significantly lower risk of dementia. • Intake of spirits not linked to dementia. • Study did not account for dietary habits or supplement use; wine drinkers may have better diets. Truelson, et al, Neurology 2002;59:1313-1319
Hepatic encephalopathy Alzheimer type 2 astrocytes
Enlarged nuclei; no reactive cytoplasm
“Ordinary” reactive Astrocytes
Kernicterus = nuclear jaundice
Kernicterus = nuclear jaundice
Diagnosis?
Wilson’s Disease One of Wilson’s Original Patients
Before onset of symptoms
Two years later
Wilson’s Disease • Disorder of Copper Metabolism • Ingested copper is absorbed in the proximal small intestine; bound to albumin in portal circulation and taken up by hepatocytes. • ATP7B in hepatocytes is involved in: – excretion into bile (no enterohepatic circulation), or – incorporation of copper into ceruloplasmin • If ATP7B is deficient, less excretion & incorporation • Copper accumulates beyond cellular storage capacity • Hepatocytes are damaged by excess copper • Copper (unbound) is released into circulation, extracted by kidneys, and deposited in kidneys, brain and cornea.
Wilson’s Disease Cirrhosis
Copper deposits and damage in putamen and globus pallidus
Kayser-Fleischer ring Copper deposit in Descemet’s membrane of cornea
