CNS Degenerative disorders… “Each individual creature on this beautiful planet is here to fulfill a particular role. We are all born with a divine fire in us. Our efforts should be to give wings to this fire and fill the world with the glow of its goodness. - Wings of Fire: An Autobiography of Dr. APJ Abdul Kalam, President of India.
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“Each individual creature on this beautiful planet is here to fulfill a particular role. We
are all born with a divine fire in us. Our efforts should be to give wings to this fire
and fill the world with the glow of its goodness.
- Wings of Fire: An Autobiography of Dr. APJ Abdul Kalam, President of India.
CNS Degenerative disorders…
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CPC11-3.4 – Mrs. J.G. 75 year old housewife. Husband Bob, aged 75, who is a retired
accountant. I seem to be forgetting, can’t remember where she
parked the car. couldn’t remember our friends’ names, she repeats things all the time..
I don‟t want to be a burden. Sleep disrupted, often up during early hours of morning. P/H: well known in the community, active, social, popular,
intelligent … Kessler Psychological distress score K10: 36/50 * Mini mental state examination MMSE: 30/30 * Word list task : recall of 2 words after 20 minutes…?
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2010: Helena, 65y Fem. Helena is a 65 year old married local GP. She is
known as a ‘pillar of the community’ and works full time as the senior partner at a GP surgery in Townsville. She is actively involved in many GP related educational activities. Her husband, Brad, is a local orthopedic surgeon. Although you have been their GP for sometime, they seldom consult you. Today they have booked a double appointment with you. Brad : ‘I’ve come with Helena to discuss some
memory problems she seems to be having’ Helena : “I hope it’s nothing; Brad has always been a
worrier’
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CPC 34: Clinical Not sleeping well, I think memmory is a bit
worse- it’s stress and fatigue’ can’t remember where she parked the car She has forgotten social arrangements
several times Couldn’t remember their names … she is struggling with organizing…
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CPC34 – Clinical Duration of symptoms: ? about 6/12 Mood: low, quite tearful at times; not enjoying life
much. Concentration: poor, struggling to read
books/journal.. Sleep: disrupted, often up during early hours of
morning. Appetite and weight: no change I am very tired. It’s probably time for me to
Broca’s area - Cingulate and Parahippocampal gyri.
Hippocampus: where short-term memories are converted to long-term memories
Thalamus: receives sensory and limbic information and sends to cerebral cortex (cognition)
Limbic system: controls emotions and instinctive behavior (includes the hippocampus and parts of the cortex)
10 – 10 – 10minutes months years
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"I wasn't living my life. My life was living me. I realised I made many of my decisions without thinking their consequences…“I realised all I really had to do to reclaim my life was to Start making decisions by considering their consequences in the immediate present, near term and distant future.. i.e . In ten minutes, in ten months and in ten years”.
-- Suzy Welch.The 10-10-10 rule.
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Pathology of C.N.S. Degenerative
Disorders
Dr. Venaktesh M. ShashidharA/Prof. & Head of Pathology
James Cook University
CNS Degenerative disorders…
CNS Degenerations Increasing incidence – Ageing. Affect functional groups of neurons. Accumulate abnormal proteins. Primary & Secondary, Global & Local types. Dementia – Acquired defect in higher function:
Memory, language, insight & planning.. “Human” > 45% of adults over 85y are demented…!
Alzheimer’s disease: Commonest cause of dementia in elderly Sporadic common (>60y) familial ~10% early. insidious onset of impaired higher intellectual function,
altered mood and behavior, progress to disorientation, memory loss, aphasia disabled, immobile… ~25y.
Alzheimer’s disease: Genetics Autosomal dominant genetic pattern – rare 10% 4 genes on chromosomes 1, 14, 19, and 21, influence
initiation and progression. Chromosome 21 generates the precursor protein for
the amyloid protein (APP). Trisomy 21 produces early Alzheimer's disease in persons with Down syndrome.
Chromosome 19 generates apolipoprotein (apo) some of them increase risk for Alzheimer's disease (ε4/ε4) by increasing Aβ amyloid deposition.
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Alzheimer’s – Pathogenesis: Amyloid Aβ is created when the transmembrane protein
amyloid precursor protein (APP) is cleaved by the enzymes β-amyloid converting enzyme (BACE) and γ-secretase (instead of α)
Deposition of neurotoxic Aβ around blood vessels (amyloid angiopathy) & interstitium neuritic plaques.(axonal tangles around)
Aβ also leads to hyperphosphorylation of the neuronal microtubule binding protein tau in neurons to form ‘neurofibrillary tangles’ within neurons.
Both are neurotoxic leading to Atrophy of neurons & reactive glial proliferation – gliosis.
CNS Degenerative disorders…
18• Cortical Atrophy
• Intraneuronal Neurofibrillary tangles
• Interstitial amyloid Neuritic plaques• Loss of neurons with gliosis.
Alzheimers Disease: MorphologyGross Microscopy
Neurofibrillary Tangles
Neurons have an internal support structure partly made up of microtubules. A protein called tau helps stabilize microtubules. In AD, tau breaks, causing microtubules to collapse, and tau proteins clump together to form neurofibrillary tangles.
Slide 18
Pathogenesis of
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Normal
Pathogenesis ofAmyloid Plaques
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Cerebrum stained with polyclonal antibody against βA4 peptide showing amyloid deposits in plaques in brain substance (arrow A) and in blood vessel walls (arrow B)
Alzheimer’s - Amyloid Angiopathy
Amyloid core
Dystrophic neurite
s
Silver stain
Congo Red stain
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Morphology in AD:
Plaques & around BV. NF Tangles-Intracellular Aβ Amyloid tau protein
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CNS Morphology in Alzheimer's:
A-Neuritic Plaque
, B-Amyloid
Atroph
y
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• Degenration starts in the entorhinal cortex, then proceed to hippocampus.
• Neuronal loss leads to shrinkage.
• Changes can begin 10-20 years before symptoms appear.
• Moderate signs: increased memory loss and confusion, problems recognizing people, difficulty with language and thoughts, restlessness, agitation, wandering, and repetitive statements.
AD Morphology - Mild to Moderate
Slide 21
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• Extreme shrinkage of brain.
• Patients are completely dependent on others for care.
• Symptoms: weight loss, seizures, skin infections, groaning, moaning, or grunting, loss of bladder and bowel control.
• Death usually occurs from aspiration pneumonia or other infections.
AD Morphology: Severe AD
Slide 22
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AD & Intelligence.…! In early life, higher skills in grammar and
density of ideas are associated with protection against AD in late life.
Mentally stimulating activity protects against AD.
Use it or loose it…..!
Coffee protects against Alzheimers Tea protects against Parkinsons
Age related / Senile degeneration: Age related Dementia: All spheres of
intellect affected. Decreasing mass - Slow 4th decade – rapid
7th decade. progressive neuronal loss Neuronophagia.
(hippocampus and cerebral cortex) reduction in size & numbers of dendritic
branches in surviving neurons Cortical atrophy, hydrocephalus. Thickening of leptomeninges. NF tangles, Aβ Amyloid plaques. increase in number of astrocytes Athero & artero sclerosis makes it worse.
Young
Old
Other CNS degenerations:
Local / Systems• Fronto-Temporal - Pick’s• Parkinson’s• Huntington’s
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CNS Degenerative disorders…
Fronto-Temporal Dementia Second common, Group of dementia, affecting
personality, behaviour & speech. Younger*, Memory not affected until late* Many sub types.
Pick's Disease: FTLD-tau common. FTLD-TDP43 – next common.
Semantic Dementia (understanding language) Progressive language problems Aphasia
predominate. Dementia later.
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Pick’s Disease: Severe, 40-65y, Rare. knife blade atrophy of
Frontal & temporal lobe Progressive aphasia / language dysfunction
Disorders of Myelin:Demyelinating Disorders - Multiple sclerosisDysmylinating disorders – Leukodystrophies.
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Metabolic CNS Disorders: Alcoholism induced CNS
disorders: Wernicke syndrome (vit B1
thiamine def.) – ataxia, confusion.
Korsakoff syndrome (memory)
Central pontine myelinolysis
Cortical atrophy Atrophy of vermis of the
cerebellum.
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Wernicke's encephalopathy:
Recurrent petechial hemorrhages in the hypothalamus, mamillary bodies with atrophy.Wernicke’s Sy: Altered Thermal regulation & consciousness, ophthalmoplegia, nystagmus. Korsokoff Psychosis: Loss of recent memory compensated by confabulation.
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Korsakoff's disease: Korsakoff's disease.Central pontine myelinolysis. Demyelination of the center of the pons. Shrunken, brown mammillary bodies (indicating chronic stage).Cause is unknown but usually seen in chronic alcoholics and associated with rapid over-correction of hyponatremia.
Alcoholic cerebellar atrophy. Shrunken folia and widened fissures of the anterior, superior vermis of the cerebellum. Another change which may be found in chronic alcoholics.