Pathology of CNS degenerative disorders.

1. “ 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 (1999)

7. Brain: Functional areas. Memory

8. Brocas area (1878) consists primarily of cingulate and parahippocampal gyri.

9. Hippocampus: where short-term memories are converted to long-term memories Thalamus : receives sensory and limbic information and sends to cerebral cortex Hypothalamus : monitors and controls internal clock & other activities. Limbic system : controls emotions and instinctive behavior (includes the hippocampus and parts of the cortex) Functional Neuro Anatomy Slide 8

10. Dendritic tree - vs - Intelligence Rat CA1 pyramidal cell labeled with EGFP (Two photon laser scanning microscopy) Synaptic bouton in rat CA1 stratum radiatum (Electron microscopy)

11. What is Success? "To laugh often and much; to win the respect of intelligent people and the affection of children. To leave the world a better place. To know even one life has breathed easier because you have lived… that is success..! -- Ralph Waldo Emerson

12. Pathology of C.N.S. Degenerative Disorders Dr. Venaktesh M. Shashidhar A/Prof. & Head of Pathology James Cook University

19. Alzheimers Disease: Cortical Atrophy Neurofibrillary tangles & Extraneuronal Neuritic plaques

21. Generation of Amyloid ( Aβ) Plaque Normal

22. Alzheimer’s - Amyloid Angiopathy Cerebrum stained with polyclonal antibody against βA4 peptide showing amyloid deposits in plaques in brain substance (arrow A) and in blood vessel walls (arrow Amyloid core Dystrophic neurites

24. Neurofibrillary Tangles in AD: C: Neurofibrillary tangles (arrowheads) are present within the neurons (H & E). D: Silver stain showing a neurofibrillary tangle within the neuronal cytoplasm

25. Alzheimer’s - Amyloid Angiopathy Congo Red stain & Polarised Microscopy showing apple green” birefringence

26. Neuron degeneration- granulovcuolar. Several neurons display granulovacuolar degeneration of the cytoplasm. B. A neuron (center) contains an eosinophilic Hirano body (arrow).

27. Cerebral atrophy in Alzheimer's: A-Neuritic Plaque, B-Amyloid

28. Cerebral atrophy in Alzheimer's:

29. Knife blade Fronto-temporal atrophy in Picks.

30. Cerebral atrophy in Alzheimer's:

31. Cerebral atrophy in Alzheimer's:

32. Cerebral atrophy in Alzheimer's: Severe cortical atrophy, narrow gyri, wider sulci. White matter loss leading to dilated ventricles (compensatory hydrocephalus). Hippocampus Atrophy

36. Neurofibrillary Tangles in AD: Plaque around Blood Vessels. Neurofibrillary Tangles -Intracellular A β Protein Amyloid tau protein – Microtubule.

39. Picks Disease: Knife blade Fronto-temporal atrophy

44. Huntington’s

45. Normal - Huntington’s Striatum Atrophy

46. Huntington’s

47. Huntington’s

51. Parkinson’s: The pigmented neurones in the substantia nigra within the midbrain degenerate and die off in Parkinson's disease, giving a pale appearance in comparison to an age-matched normal control. Normal Parkinson’s

52. Parkinson’s: Surviving neurone in the substantia nigra contains an intracytoplasmic Lewy body (L). Normal

53. Parkinsons disease: Lewy body

55. System Degenrations: Unknown Ataxia Sensory loss Tremor Orthostatic hypotension Substantia nigra Purkinje cells Pontine nuclei Spinal autonomic nuclei Multiple system atrophy ( Shy-Drager syndrome ) CAG triplet expansion in gene on 12p Chorea Myoclonic epilepsy Dementia Autosomal dominant inheritance Dentate nucleus Globus pallidus Subthalamus Red nucleus Dentatorubro-pallidoluysial atrophy ( DRPLA ) CAG triplet expansion in ataxin-1 gene on 6p Ataxia Nystagmus Autosomal dominant inheritance Purkinje cells Granular neurones Inferior olivary nuclei Autosomal dominant cerebellar ataxia type 1 CAA triplet expansion in frataxin gene on 9q Ataxia Sensory loss Deafness Autosomal recessive inheritance Spinal cord Sensory nuclei Cerebellum Friedreich's ataxia Genetic basis Clinical features Sites affected Disease

56. The only real mistake is the one from which we learn nothing. JOHN POWELL:

60. Multiple Sclerosis Plaque: Section of fresh brain showing brown plaque around occipital horn of the lateral ventricle.

61. Multiple Sclerosis: Demyelinated plaques Microscopy showed loss of myelination with many lipid macrophages.

62. Multiple Sclerosis - plaques

63. Multiple Sclerosis - plaques

64. MS – Periventricular plaque MS Like patches of grey matter within white matter…! Normal

65. MS- Plaques – Myelin stain.

68. 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.

69. Korsakoff's disease: Note: Shrunken, bodies brown mammillary bodies indicating chronic stage or Korsakoff's disease. Central pontine myelinolysis. Demyelination of the center of the basis pontis. Cause is unknown but is usually in chronic alcoholics and is often 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.

71. Pathology of CNS degenerations: Intracytoplasmic α-Synuclein Lewy bodies Parkinson disease Intracytoplasmic tau Glial inclusions Multiple system atrophy Intracytoplasmic tau Neurofibrillary tangles Frontotemporal dementias (Pics disease) Intracytoplasmic α-Synuclein Lewy bodies Dementia with Lewy bodies Intracytoplasmic Neurofilament subunits/super-oxide dismutase (SOD-1) Spheroids Amyotrophic lateral sclerosis Extracellular Intracytoplasmic β-Amyloid tau Senile plaques & Neurofibrillary tangles Alzheimer disease Location Components Lesion Disease

72. Anybody who thinks money will make you happy, hasn't got it….!

91. "Education is for ‘life’.. not for mere ‘living’ "The end of education is character" - BABA

93. MND: Atrophy of anterior nerve roots.

103. Brain Activity: PET Scan (language skills) Hearing Words Speaking Words Seeing Words Thinking about Words Different mental activities take place in different parts of the brain. Positron emission tomography (PET) scans can measure this activity. Chemicals tagged with a tracer “light up” activated regions shown in red and yellow. Slide 13

104. Neuro Anatomy - Function