neurobiology of neuroglia Applied Joy.pptx

neurobiology , cells of CNS . Neuroglia . neuron

1. Neurobiology of Neuron and neuroglia (Applied) DR.K.M.NAZMUL ISLAM JOY MD NEUROLOGY THESIS PART STUDENT DEPARTMENT OF NEUROLOGY DMCH

2. We will discuss DISEASES OF NEURON DISEASES OF NEURGLIA NEW FRONTIER

3. Epilepsy and seizure Seizure : A paroxysmal event due to excessive, abnormal, hyper-synchronized electrical discharge from cerebral neurons manifested as motor, sensory, autonomic or psychiatric manifestations with or without loss of consciousness. Epilepsy: Epilepsy is the clinical condition in which a person has recurrent seizures ( two or more unprovoked seizures ) due to a chronic underlying process.

4. Epilepsy and seizure

5. Types and pathophysiology PRIMARY EPILEPSY SECONDARY EPILEPSY No underlying structural defect is expected. Underlying structural defect is expected, detectable or not. Electrical discharges originates from diencephalic activating system and spread simultaneously to all areas of cortex. Originates from a paroxysmal discharge in a focal area of cerebral cortex; may subsequently spread to rest of brain by diencephalic activating pathway. Age between 8-30 years Onset <5 or >50 yrs May be positive family history Family history absent

6. PRIMARY EPILEPSY SECONDARY EPILEPSY No history suggestive of structural abnormality History suggesting of structural abnormality-birth trauma, head injury, stroke, brain surgery No MR/CP Associated MR/CP No aura Presence of aura Generalized onset, attack is generalized. Focal onset, focal features during attack. No post ictal paralysis Presence of post ictal palsy

7. Primary generalized epilepsy

8. Secondary epilepsy-EEG

9. Causes of secondary epilepsy Mesial Temporal Sclerosis(Right) Glioma (left sided)

10. Causes of secondary epilepsy axial sections showing FCD in the frontal lobe

11. Causes of secondary epilepsy

12. Vascular diseases

13. Vascular diseases

14. Developmental disabilities Cerebral Palsy Intellectual disability Autistic Spectrum Disorder Learning disabilities

15. Cerebral Palsy Germinal matrix hemorrhage in premature infants. Periventricular leukomalacia (PVL) Hypoxic –ischemic damage Spastic Dystonic Ataxic Hypotonic Mixed Choreo-athetoid

16. INFECTIVE DISEASES

17. Infections of neuron Meningitis: Inflammation of pia and arachnoid mater along with the subarachnoid space. Encephalitis : Inflammation of brain parenchyma by viral infection. Cerebritis : Focal infection of brain tissue devoid of capsule. Brain Abscess: Focal , suppurative infection within brain parenchyma typically surrounded by a vascularized capsule.

18. Causes of meningitis (Infective) Bacterial: N.meningitidis S.pneumoniae H.influenzae Group B streptococci Gram negative bacilli( E.coli ) M.tuberculosis Viral : Enterovirus Mumps Herpes simplex VZV EBV HIV Mollaret’s meningits Fungal : Cryptococcus neoformans Candida Histoplasma Protozoa/parasite : Toxoplasma Amoeba

19. Causes of meningitis (Non-Infective) Malignancy: Bronchial carcinoma Breast cancer Leukemia Lymphoma Inflammatory : SLE Sarcoidosis Behcet’s Disease

20. Other infections Bacterial: Epidural abscess/ Pott’s Neurosyphilis Lyme disease Tetanus Viral : TM Poliomyelitis SSPE PML Protozoal / Helminths : Cerebral malaria Cysticercosis Prion disease : CJD--- sCJD,fCJD,iCJD,vCJD FFI Kuru GSS

21. Clinical scenario-1 20 years old male Diffuse, dull aching, persistent headache for 3 months More on morning and increased on bending & coughing. Vomiting. Bradycardia Hypertension Raised ICP headache due to ICSOL

22. Brain edema

23. Vasogenic edema: Incompetent blood-brain barrier Causes : Infections, trauma, tumor Cytotoxic edema: Cellular swelling Causes : Toxic, metabolic, ischemia, trauma Interstitial edema: Obstructive hydrocephalus Brain edema Clinically significant brain edema represents a combination of vasogenic and cellular components. Brain edema raises ICP leading to reduced cerebral perfusion and ischemia. Brain edema can cause “coning” and sudden death.

24. Degenerative disease of the neurons CNS Parkinsons disease Motor neuron disease Huntington’s disease Alzheimers disease Motor neuron disease

25. Degenerative disease of basal ganglia and brainstem Parkinsons disease Huntingtons disease

26. The n parkdopaminergic neurons of the substantia nigra project to the striatum and their degeneration in Parkinson’s disease is associated with a reduction in the striatal dopamine content. The severity of motor syndrome is proportional to the dopamine deficiency

27. Degenerative diseases of Neurone (PD) Bradykinesia Tremor Rigidity Postural instability In PD there is extensive degeneration of the dopaminergic neurons of the substantia nigra.

28. Degenerative diseases of Neurone (PD)

29. Degenerative disease of CNS ( PD )

30. Degenerative diseases of Neuron (HD) 40 years old male Generalized choreo-athetoid movement for 3 years Dementia Father had same illness . Abnormal Huntingtin protein accumulation in neurons Neuronal loss in caudate nucleus.

31. Degenerative diseases of Neuron (AD)

32. Alzheimer's disease (AD) Loss of hippocampal and cortical neurons leads to impairment of memory and cognitive ability Short term memory loss Apraxia Aphasia Anosognosia Depression Impaired cholinergic transmission/NA/5HT/Glutamate

33. Elderly male Progressive weakness of 04 limbs for 6 months Spastic quadriplegia with wasting of limbs No sensory problems No bowel bladder problem MRI C/S is normal. Degenerative diseases of Neuron (MND)

34. Degenerative diseases of Neuron ( mnd )

35. Demyelinating diseases CNS: Multiple Sclerosis Neuromyelitis optica ADEM PNS : GBS CIDP MMN

36. Demyelinating disease of the CNS Multilple sclerosis Acute demyelinating encephalomyelitis Neuromyelitis optica ODS

37. Demyelinating Disease (MS) 30 years old lady Recurrent attacks of- Vertigo Tendency to fall towards right side Dimness of vision INO Nystagmus Cerebellar signs on rt Bilateral plantar extensor

38. Demyelinating Disease (MS)

39. Nerve trauma Saturday Night Palsy (Wrist Drop)

40. Mechanism of CNS injury Two major types of forces are responsible for traumatic brain injury 1. localized at the site of impact – contact phenomena generates superficial and contutional trauma through coup and countercoup mechanism 2.rotational forces – axonal shearing occurs commonly due to acceleration- deceleration injury Shearing injury may also damage blood vessels and cause petechial hemorrhage , deep intracerebral hematoma and brain swelling

41. In head injury patients, the extent of neurological recovery depends on post traumatic secondary insults. These includes – Hypotension Hypoxia Anaemia Hyperglycaemia Sepsis and Hyperthermia ( bradly an

42. Traumatic neuronal damage Diffuse axonal injury Diffuse axonal injury is characterized by severe head injury that rapidly progresses to come in the absence of specific focal lesions Diffuse axonal injury (DAI) , also known as  traumatic axonal injury (TAI) , is a severe form of  traumatic brain injury  due to shearing forces MRI especially SWI sequence will the most sensitive imaging modality to diagnose DAI. CT may be false negative

43. Nerve trauma In CNS, degeneration is NOT followed by regeneration. In PNS, section of an axon is followed by attempts at regeneration with reparative changes taking place in the body.

44. Diseases at synapse

45. Diseases at synapse

46. Tumors of Neurons Tumor of neurons in the CNS are rare but not uncommon in PNS Neuroblastoma Ganglioneuroma Pheochromocytoma

47. Disorders of neuroglia Response to injury: Mediated by Astrocytes with fibrosis : Gliosis . Follows any significant tissue destruction Post infective Post inflammatory Post stroke or trauma May be epileptogenic .

48. 60% of primary brain tumors are glial tumors. Of which 80% are malignant. Tumors of neuroglia Brain tumors …. … . Primary Secondary ….. Glial-80% Meningioma -25% Vestibular schwannoma-10% Primary CNS Lyphoma-2% Glial tumors: Astrocytoma Oligodendroglioma- (15-20%) Ependymoma

49. Astrocytoma Infiltrative tumors 04 types- Grade I- Pilocytic astrocytoma Grade II- Diffuse astrocytoma Grade III- Anaplastic astrocytoma Grade IV- Glioblastoma (Commonest malignant primary) Grade I- Children+Young Grade II- do Grade III- 4 th /5 th decade Grade IV- 6 th /7 th decade Common locations : Cerebral hemisphere Brain stem Cerebellar hemisphere Hypothalamus

50. Astrocytoma Mixed intensity Contrast enhancement (ring like) Ill-defined Perilesional oedema Mass effect

51. Astrocytoma

52. Astrocytoma Maximal safe surgical resection Radiotherapy Adjuvant chemotherapy Grade-I-potentially curable Others-recurrent Median survival 14.6 months

53. Oligodendroglioma Age : 30-50 Years Common location : Cerebral hemisphere(frontal lobe) MRI Features: Well defined Calcification is common Absence of necrosis Non-contrast enhancing Edema is minimum Prognosis : Better (10 years) with Rx.

54. Ependymoma Childhood tumor (5% of childhood tumors) Location : Fourth ventricle (posterior fossa ) Myxopapillary filum terminale - in adult Treatment Surgical resection Radiotherapy Prognosis : Good if totally resected.

55. Moving Forward: Can Neurons regenerate?

56. S tem cells hold tremendous promise for neurodegenerative diseases or injury. Medical application is still in infancy.

57. Colllection & culture of human embryonal stem cells. Reprogramming adult human endogenous stem cells with transcription /growth factors. B one marrow stromal cells have been injected to blood after stroke and seem to produce a tropic factor for enhancing plasticity. Stem cell research

58. Thank You all!