CNS lecture Dr.Mai.pptxhttps://www.slideshare.net/slideshow/embolism-154443210/154443210

Cns dr.mai

1. Diseases of the CNS Dr.Mai Inbiek

2. Subjects: Increased intracranial pressure Hydrocephalus Cerebral edema Vascular diseases Vascular malformation CNS trauma Infections of CNS Neoplasms of CNS Neoplasms of peripheral nervous system

3. Increased intracranial pressure Causes: - Disorders that may cause dangerous increases in the volume of intracranial contents include: Generalized cerebral edema, hydrocephalus, hemorrhages, ischemia, and mass lesions such as tumors. Herniation Is the displacement of brain tissue from one compartment to another in response to increased intracranial pressure.

4. Hydrocephalus increase in the volume of the CSF within the ventricular system. Is a consequence of impaired flow or decreased absorption of CSF lead to abnormal dilatation of ventricles and pressure atrophy of brain.

5. Effects of hydrocephalus: - Brain atrophy - Head enlargement ,If hydrocephalus develops in infancy before closure of the cranial sutures. - increased intracranial tension:- Severe headache Projectile vomiting Papilledema (swollen optic disc) Herniation of the brain Hemorrhage Edema

6. Cerebral edema It indicates accumulation of excess fluid within the brain parenchyma. There are two types, 1-Vasogenic edema: Due to disruption of integrity of normal blood brain barrier, so fluid escape from blood vessels to interstitial spaces of brain. (intravascular extracellular). The absence of significant lymphatic drainage impairs reabsorption of excess water. A - localized in cases of abscess or tumors(due to increased vascular permeability). B - generalized in cases of sever head trauma, malignant hypertension.

7. 2-Cytotoxic edema: Due to increased intracellular fluid secondary to neuronal and glial cell injury in generalized hypoxic-ischemic insult or exposure to certain toxins. ---► abnormalities in ion transport ---► increased amount of water within the cell Intracellular odema . The two types of odema , often occur together, particularly after generalized injury.

8. Morphology: Edematous brain is softer than normal & overfill the cranial vault. In generalized edema, gyri become flattened, sulci are narrowed & ventricular cavities are compressed. Herniation may occur.

9. Cerebrovascular diseases. I- Ischemic brain damage: a . Global hypoxic, ischemic- encephalopathy. b. Focal : infarcts. (70-80% of cerebro -vascular accidents) II-Intracranial hemorrhages: Primary intracerebral haemorrhage and subarachnoid haemorrhage I-Ischemic brain damage a. Global hypoxic, ischemic- encephalopathy: Causes: Ge neralized reduction in blood flow due to decrease of blood pressure below 50 mmHg ----► severe hypoxemia ,inadequate autoregulation , results in rapid fall in cerebral perfusion as in cardiac arrest, shock, sever systemic hypotension . Neurons are highly susceptible to hypoxic damage, more than glial cells.

10. The resulting deficits range from mild , transient neurologic disturbances, to brain death (diffuse cortical injury) brain autolysis so called respirator brain . Morphology : Gross: After 48hr , soft, swollen brain with wide gyri and narrowed sulci and the cut surface   shows poor demarcation between gray matter and white matter. -Areas of watershed infarct (border zone ) wedge-shaped necrosis (occur in regions of   the brain and spinal cord that lie at the most distal portions of arterial territories).

11. U/M : -Early changes -12-24hr acute neuronal cell change in form of eosinphilic cytoplasm and pyknotic nuclei ( red neurons ). - Subacute changes , after 24-48 hours ---►infiltration by neutrophil, necrosis of tissue, macrophage influx. -Repair seen after 2weeks characterized by reactive gliosis.

12. b-Cerebral infarction (focal cerebral ischemia) Common in old male, 70 years, due to local vascular obstruction. Causes : Cerebral arterial occlusion leads first to focal ischemia and then to infarction in the distribution of the compromised vessel. 1-2-Embolic infarction: (commonest cause) , cardiac origin, and commonly affecting middle cerebral artery . 2-Thrombotic occlusions: Commonly due to atherosclerosis, common sites are the carotid bifurcation, the origin of the middle cerebral artery, and either end of the basilar artery . 3- Vasculitis & trauma. -

13. Morphology: Gross : Two types: -Hemorrhagic infarct ( due to reperfusion of ischemic tissue, either through collaterals or after dissolution of emboli ). Manifest as multiple, petechial hemorrhages. -Non hemorrhagic infarct (due to acute vascular occlusions ): -By 48h,the tissue becomes pale, soft ,and swollen. - From days 2 to 10, the injured brain turns   gelatinous and friable. - From day 10 to week 3 ,the tissue liquefies leaving fluid filled cavity. This is an infarct in the distribution of the middle cerebral artery.

14. Histopathologic progression of CNS infarcts B- “RED ” NEURONS ( eosinophilic cytoplasm , and    nuclear pyknosis and karyorrhexis ) D- MONO’s (MACs ) E- GLIOSIS A- Odema C- POLYs

15. U/M: Cell death occurs within minutes, but morphologic changes appears after 8-12 hours ischemic necrosis (red neurons), PNL infiltrate, edema & hemorrhage . 3rd day macrophages appear to phagocytose necrotic debris with vascular proliferation. By one month liquefaction of infarct irregular cavities(old cystic infarcts) with peripheral fibrillary gliosis (astrocytes at the edges of the lesion enlarge, divide    a prominent network of cytoplasmic extensions dense network of glial fibers   admixed with new capillaries and a few perivascular connective tissue fibers) (Note : Lacunar infarcts: When thrombotic occlusions causing small infarcts of only a few millimeters in diameter , usually from long-standing hypertension).

16. II- Intracranial hemorrhages: a-primary haemorrhage in the brain parenchyma ( intracerebral haemorrhage ). b- Haemorrhage in the subarachnoid space ( subarachnoid haemorrhage most commonly due to rupture of aneurysm).

17. A- Primary parenchymal hemorrhages (intracerebral hemorrhage) Second most common cause of stroke ( after atherosclerosis). Common in mid to late adult life, with a peak incidence at about 60 years of age. Causes: 1- Hypertension accounts for 50% of cases. Hypertension ---► Accelerated atherosclerosis , hyaline arteriolosclerosis ,proliferative changes and necrosis of arterioles ---► rupture ---► hemorrhage (the common sites are the region of the basal ganglia, ,thalamus, pons and the cerebellum). 2-Cerebral amyloid angiopathy (CAA), cagulation disorders, vascular malformations, tumor.

18. Morphology: Gross : Hemorrhage may extend to brain parenchyma (compression) and later form a well localized hematoma, that is absorbed over time leaving a fluid filled cavity with brown rim( apopleptic cyst ).   Microscopic: Clotted blood surrounded by edematous brain tissue. The cellular events follow the same time course  observed after cerebral infarction .   Hemorrhages involving the basal ganglia area tend to be non-traumatic and caused by hypertension, which damages and weakens the small penetrating arteries. A mass effect with midline shift, often with secondary edema, may lead to herniation.

19. Vascular malformations : Are important cause of intracranial hemorrhage, specially in young patients. Types : Arteriovenous malformations (most common) Capillary telangiectases . Venous & cavernous angiomas The intraventricular and intracerebral hemorrhage seen here was due to a ruptured vascular malformation.

20. b- Subarachnoid heamorrhage & saccular aneurysm : Haemorrhage caused by rupture of saccular aneurysm. Saccular (berry aneurysms) occur in 2% of population . 80% occur in anterior circulation at the bifurcation in the branches of the internal carotid artery (between anterior cerebral & anterior communicating arteries), and 20% occur with branches of posterior circulation ( vertebrobasilar ). There is congenital defect in the media of arteries at the branching points . Etiology unknown, sporadic , genatic common in patients with polycystic kidney disease, coarcatation of the aorta & arteriovenous malformation.

21. Morphology: Saccular aneurysms are usually small, less than 3mm, multiple in 30% of cases. The wall of the aneurysm shows no media, and lined only by thickened intima ,lumen may contain laminated thrombus. Rupture ---► releasing blood into subarachnoid space or brain substance ,or both. Healing by scar may obstruct CSF hydrocephalus. rupture of a saccular aneurysm occurs at the time of an acute increase in intracranial pressure causing sudden sever headache(the most important sign),and death in 25 % and 50% of affected individuals . The subarachnoid hemorrhage from a ruptured berry aneurysm carry a risk for ischemic injury from vasospasm of other vessels.

22. Central nervous system trauma Traumatic Vascular Injury 1-Epidural hematoma : A ccumulation of blood between the dura and the skull. Cause: Traumatic tear of middle meningeal artery in skull fracture (or easily deformable skull in infants) (arterial cause). A blood clot is seen over the external surface of the dura . Thus, this is an epidural hematoma. Such a location for hemorrhage is virtually always the result of trauma that causes a tear in the middle meningeal artery

23. Effects: Epidural hematoma strip the dura from the inner skull surface and compresses the brain surface. If not immediately drained, herniation effects & brain stem compression & death may occur. Many patients ---► lucid interval followed by loss of consciousness .

24. 2-Subdural hematoma: Accumulation of blood between dura and subarachnoid. Caused by disruption of bridging veins that extend from surface of brain to dural sinuses(vinous cause),elderly persons with brain atrophy &infants are more susceptible. a- Acute ; Appear as large fresh hematoma,and underlying brain is flattened. -About 1 week ---► hematomas organize by lysis of the clot.   -2 weeks growth of granulation tissue and, in 1–3months fibrosis.   -Slow symptoms than epidural hemorrhage. b- Chronic ; rebleeding from the thin- walled vessels of granulation tissue --- ► altered mental state & focal neurologic deficits(surgical removal).

25. The dura has been reflected above to reveal the bridging veins that extend across to the superior aspect of the cerebral hemispheres. These can be torn with trauma, particularly if there is significant cerebral atrophy that exposes these veins even more. The dura has been reflected back (with a small portion visible at the lower right) to reveal a subdural hematoma. Such a blood clot is usually the result of trauma with tearing of the bridging veins

26. Infections of the CNS Meningitis ( lepto and pachy ) ,encephalitis (cerebritis, cerebral abscess). Meningitis ( Leptominigitis ) Acute purulent leptomeningitis : (bacterial) Aseptic (viral) meningitis Chronic meningitis

27. Acute purulent leptomeningitis : (bacterial) It is acute infection of the pia -arachnoid. Causative organisms: Neonates: Beta-streptococci , E-coli , listeria. ( BEL ) Children older than 2 years: H.influenza , strept.pneumonia . Neisseria meningitides in older children, adolescence & young adults. Strept . pneumonia in older adults(most common cause ) Listeria& klebsiella in immunocompromised patients. Route of entry : 1-Hematogenous spread, as in bacterial endocarditis, lung abscess, bronchiectasis, pneumonia. 2-Contiguous spread from adjacent focus (sinusitis, otitis media). 3-Direct implantation of organisms in trauma. .

28. Morphology : Grossly: Meninges are congested , thick and opaque with presence of creamy purulent exudates in subarachnoid space. CSF turbid to frankly purulent, contain PNL, increase in protein content, decrease in glucose content, bacteria are present . Fulminant miningitis may cause focal cerebritis , brain abscesses,or ventriculitis . A thick layer of suppurative exudate covers the brainstem and cerebellum and thickens the leptomeninges

29. U/M : Leptomeninges are congested, infiltrated by PNL & fibrin. In untreated cases gram stain reveals causative organism Acute purulent leptomeningitis a neutrophilic exudate is seen involving the meninges at the left, with prominent dilated vessels.

30. Aseptic meningitis (viral meningitis ) Self- limited disease and has better prognosis than suppurative type and symptoms are less severe than bacterial. Causes : Echovirus, Coxsackie's virus, mumps virus, HIV. CSF shows: ● Mild increase in protein content . ● Normal glucose. ● Lymphocytosis. Chronic meningitis : TB, spirochetal infections, cryptococcal (with AIDS).

31. Encephalitis: Refers to inflammation of the brain parenchyma. It is may be the result of bacterial, viral, fungal and protozal infection. Brain abscess(localized ,capsulated), cerebritis(localized, without capsule). A- Brain abscess: Causative organism: Streptococcal, staph,… Route of entry : -Hematogenous spread, contiguous spread from adjacent focus (sinusitis, otitis media), direct implantation of organisms in trauma.

32. Morphology: Grossly Solitary( or multiple especially in hematogenous spread). Localized area of inflammatory necrosis with yellow pus, and edema surrounded by fibrous capsule. U/M Liquefactive necrosis containing pus, surrounded by acute and chronic inflammatory cells, neovascularization, edema ,fibrous capsule surrounded by reactive gliosis.

33. Chronic Brain Abscess Smooth wall (Fibrous Tissue) Acute Brain Abscess Liquifactive center filled with pus Shaggy irregular necrotic wall Surrounded by a zone of congestion

34. Clinically: Fever & neurologic symptoms. CSF ---► White cell count and protein levels are high, but normal glucose . Complications : Increased intracranial pressure(ICP), brain herniation(fatal). Rupture of abscess into ventricles or subarachnoid space can lead to ventriculitis , and meningitis.

35. B- Tuberculous encephalitis: Complicate pulmonary TB. Affect meninges or brain substance with single or multiple tuberculomata . C- Toxoplasmosis: Common in AIDS patients. Areas of necrosis & mononuclear inflammation.

36. D- Viral encephalitis - It is the most common cause of encephalitis. most sever -Rabies virus, Poliovirus, Arbovirus , HSV, CMV, HIV,…. -It is usually associated with meningitis ( meningoencephalitis ). U/M Multiple foci of necrosis of gray and white matter are found. Perivascular infiltrate by lymphocytes, plasma cells & macrophages. Viral inclusion bodies within infected cells as Negri bodies in rabies. Microglial nodules Microglial cells form small aggregates around foci of necrosis . Neurophagia ( s in gle-cell neuronal necrosis with phagocytosis of the debris ).

37. Characteristic findings of viral encephalitis include perivascular cuffs of lymphocytes (A) and microglial nodules (B).

38. HIV encephalitis(AIDS-Dementia Complex) Patients may have acute viral meningitis, or subacute AIDS encephalitis . U/M: Groups of macrophages, lymphocytes, and multinucleated giant cells cluster in the white matter & basal ganglia.

39. Neoplasms of the CNS 1-Primary neuroglial tumors ( gliomas ) Astrocytoma (account for about 80% of adult Gliomas) Oligodendroglioma ( 5% to 15% of gliomas ) Ependymoma 2- Primary neuroectodemal tumors(PNET) Medulloblastoma, Neuroblastoma Ependymoblastoma 3-Meningiomas 4-Nerve Sheath Tumours : Schwannoma, Neurofibroma , malignant nerve sheath tumour . 5-Metastaic tumors (the commonest) 6-Lymphoma

40. Oligodendrocyte

41. Gliomas :- All tumors arising from neuroglia. Most common primary CNS tumors. Rarely metastasize outside the CNS (even the most highly malignant Gliomas). Even low-grade lesions may infiltrate large regions of the brain. The anatomic site of the neoplasm can influence outcome independent of histologic classification due to local effects . The subarachnoid space provides a pathway for spread (seeding along the brain and spinal cord can occur in highly anaplastic as well as in well-differentiated neoplasms that extend into the CSF).

42. Astrocytoma Common in adults, in cerebral hemispheres (80%of adult brain tumors). Histologic types: 1-Diffuse astrocytoma ( Grade II ) Grossly , Poorly defined, infiltrative lesions distorts the underlying brain tissue.

43. U/M: low-grade neoplasia ,with increased number of irregularly distributed astrocytes. Nuclei are mildly atypical. Stroma is fibrillary due to an intervening network of fine ,  glial fibrillary acidic protein ( GFAP positive) astrocytic   cell processes with microcystic changes. This astrocytoma demonstrates increased cellularity and mild pleomorphism , as compared to normal brain ,with fibrillary background.

44. 2- Anaplastic astrocytoma(Grade III) U/M: There is increased cellularity, nuclear pleomorphism and hyperchromatism , mitotic activity and proliferation of vascular endothelium.

45. 3- Glioblastoma multiforme (GradeIV) Grossly , variation of the tumor from region to region , irregular, diffuse, infiltrative mass with areas of hemorrhages, necrosis & cystic changes. -The prognosis is very poor . Glioblastoma commonly spread through CSF in the subarachnoid space to the spinal cord.

46. U/M: Highly anaplastic and cellular with polymorphic cells(fusiform cells, small round cells, pleomorphic cells , and gaint cells). Characterized by microvascular proliferation , necrosis & tumor giant cells. Necrosis surrounded by dense clusters of neoplastic cells ( pseudopalisading ) . (nuclear pseudo palisading)

47. Pilocytic astrocytoma Common in children. Relatively benign behavior, grade I , non infiltrative. Site; cerebellum ,III ventricle & optic nerve. Morphology: Grossly , Cystic, with a nodule in the wall of the cyst; if solid, it is usually well circumscribed, U/M; tumor cells have elongated hair-like processes (GFAP + ve ), cystic areas & esinophilic granular bodies Rosenthal fibers are present. Pilocytic astrocytoma, arrow points to Rosenthal fibers Pilocytic astrocytoma in the cerebellum

48. Oligodendroglioma It detected in forth and fifth decades of life, in cerebral hemisphere with a predilection for white matter . Morphology : Grossly: Soft, gelatinous, infiltrative mass with cysts and calcifications (in 90% of cases). U/M: The sheets of regular cells have round uniform nuclei   containing finely granular chromatin ,surrounded by a clear halo of cytoplasm (fried-egg appearance), foci of calcification may present. Hemorrhage may be noted with network of anastomosing capillaries. Prognosis depends on histologic grade WHO grade II/IV . Anaplastic oligodendrogliomas (WHO grade III/IV)

49. Ependymoma Site: Within ventricular cavity or in spinal cord (lined by ependyma ). Cerebral ependymoma (IV ventricle) occur in patients below 20 years, while spinal tumors occur in adults. Morphology : Grossly: Well defined solid masses, may be papillary. large ependymoma of the fourth ventricle .

50. U/M ; Composed of uniform epithelial( ependymal) with dense fibrillary background , tumor cell may arrange around blood vessels (pseudo perivascular rosettes) or lumina (true rosettes). -WHO grade II/IV lesions, anaplastic ependymomas (WHO grade III/IV ).

51. Primitive neuroectodermal tumors (PNET) PNET; refers to neoplasms composed of primitive embryonal small round cells that may show neuronal, glial or mesenchymal differentiation. In CNS: - Medulloblastoma(20% of pediatric brain tumor). - Neuroblastoma & - Ependymoblastoma .

52. Medulloblastoma Highly malignant tumor occurs below 20 years, in cerebellum. It is spread locally and distally to lung, liver, vertebrae. Poor prognosis in untreated patients , but radiosensitive. Morphology: U|M : Small primitive cells (small blue round)with hyperchromatic nuclei & little cytoplasm. Neuronal differentiation is seen in the form of small rosettes around central fibrillar core ( Homer-Wright rosettes ) with mitosis. Well sircumscribed tumor

53. Other intracranial tumors Lymphomas (in immunosuppression). Germ cell tumors (in suprasellar & pineal region, as germinoma & teratoma ). Hemangioblastoma in cerebellum.

54. Meningioma Benign, arise from arachnoid meningiothelial cells. Common in adults, females , specially in patients with neurofibromatosis 2 (multiple meningiomas + vestibular schwannomas or glial tumors=NF2). Morphology: Grossly: Smooth firm lobulated mass attached to dura with compression of underlying brain( may cause cardiorespiratory arrest from compression of the medulla).

55. A meningioma is composed of whorled nests of oval, spindle cells. The histological types: grade I   meningothelial , fibroblastic , transitional, psammomatous , secratory , or grade II (atypical),and   grade III(malignant type). psammoma bodies Spammoma bodies is a calcium deposit

56. Metastatic neoplasms: 40-50% of brain tumors are metastatic. brain is a common site for metastasis, from( carcinoma ) cancer lung, breast, malignant melanoma, kidney and GIT. Typically occur at the junction between grey and white matter. Metastatic lesions are multicentric with well-demarcated margins both grossly and microscopically. Carcinoma may metastasize to leptomeninges ----► cranial nerve palsies. Lung Carcinoma Brain

57. Neoplasms of the peripheral nervous system Benign: 1- Schwannoma: It occur in soft tissues, internal organs, or spinal nerve roots. 10% are associated with familial NF2 ( multiple bilateral vestibular schwannomas , meningiomas , and ependymomas ). Gross : A well circumscribed encapsulated masses attached to peripheral, cranial or spinal nerves. This firm neoplasm was removed from the surface of a peripheral nerve. It is a schwannoma ( neurilemmoma ) which arises from the nerve sheath Schwann cells surrounding axons.

58. U/M: Schwannoma is formed of dense spindle shaped cells form hypercellular areas Antoni type A " & loose areas “with myxoid extracellular matrix Antoni typeB (biphasic neoplasm). Nuclei in Antoni A show orderly palisading resulting in alternating bands of nuclear and anuclear areas ( Verocay bodies ) . Vascular hyalinization , hemorrhage& cystic changes are common. Note the more cellular, dense "Antoni A" pattern on the left with palisading nuclei surrounding pink anuclear areas ( Verocay bodies). On the right is the "Antoni B" pattern with a looser pale stroma , fewer cells, and myxoid change Antoni type A Verocay bodies Antoni typeB

59. Vestibular schwannoma ( Acoustic neuroma): Is a schwannoma of the 8th cranial nerve .(multiple and bilateral is common with NF2) The mass lesion here is arising in the acoustic (eighth cranial) nerve at the cerebellopontine angle. This is a schwannoma. Patients may present with hearing loss. These benign neoplasms can be removed

60. 2- Neurofibromas : Clinically Sporadic. Or associated with NF1 (Café-au- lait spots, lisch nodules in eyes). Benign peripheral nerve sheath tumors. Produce fusiform swellings of involved peripheral nerve, may be solitary or multiple, noncapsulated . Three important subtypes: Localized cutaneous neurofibromas , Plexiform neurofibromas , Diffuse neurofibromas. U/M : Bundles of spindle cells with wavy nuclei admixed with wavy collagen bundles (shredded carrot appearance).

61. Leptomeninges (pia, arachnoid). Pachy meninges(dura)