DISEASES OF THE NERVOUS SYSTEM

1. DISEASES OF THE NERVOUS SYSTEM

2. Inflammatory diseases • Meningitis: • Meningitis means inflammation of the meningeal coverings of the brain and spinal cord. • Inflammation of the dura is rare and called pachymeningitis. • Inflammation of the pia and arachnoid is much more common, and called leptomeningitis. • The common types of meningitis are: • Septic (suppurative) meningitis. • Tuberculous meningitis. • Viral meningitis. • Syphilitic meningitis. • Chemical meningitis.

3. Septic Meningitis • Causes: • Meningococci:The commonest causative organisms and cause meningococcal meningitis. • Affects specially infants, children and young adults and takes sporadic or epidemic forms. • Droplet infection takes place from patient or carrier and causes nasopharyngitis. • The organisms in the nasopharynx invade the blood stream and are carried to the meninges and choroid plexus.

4. Streptococci, staphylococci, pneumococci and influenza bacilli: • Rare causes for septic meningitis. • They reach the meninges by the following routes: • Hematogenous from a distant septic focus. • Direct infection from sinusitis, otitis media and brain abscess. • Complicating compound fractures of the skull.

5. Pathology of Meningococcal Meningitis: • Gross Picture: • The brain is swollen and edematous. • The meningeal and cortical vessels are dilated and congested. • The subarachnoid space is filled with a yellowish purulent exudate. • The exudate is most abundant at the base of the brain and on the posterior surface of the cord due to the effect of gravity. • The ventricles are dilated and the cerebrospinal fluid is turbid as it is mixed with pus. • The ependymal lining is necrotic rough and the choroid plexus is congested.

6. Microscopic Picture: • The subarachnoid space shows dilated congested vessels. • Heavy infiltration by many polymorphs with some histiocytes, lymphocytes and plasma cells amidst scanty fibrin threads. • C.S.F. changes: • Increased intracranial tension. • Presence of many P.N.Ls., pus cells and bacteria. • Elevated protein content. • Decreased sugar content.

7. Clinically • Headache • Irritability • Stiff neck • Disturbed conscious level • Photophobia

8. Local effects and complications: • Thrombosis of the pial arteries causes infarctions in the brain and spinal cord. • Healing by fibrosis results in adhesions and obstruction of the foramina of Lushcka and Magendiewhich cause: • Compression of the cranial nerves; III, IV, VI and spinal nerve roots leading to diplopia, squint, ptosis. • Obstruction of the flow of C.S.F. leading to hydrocephalus.

9. General effects and complications: Septic thrombophlebitis causes septicemia and systemic pyemia. Blood spread of the bacteria causes’ acute bacterial endocarditis, pericarditis, empyema and arthritis. Adrenal cortical hemorrhage in severe cases causing acute adrenal cortical insufficiency (Waterhouse-Friderichsen syndrome).

10. Viral (aseptic meningitis) Less fulminate clinical course than in septic meningitis. It is self-limited and often treated symptomatically. The CSF shows: An increased number of lymphocytes. The protein elevation is only moderate. Glucose content is nearly always normal. Commonly due to enterovirus infection.

11. Tuberculous Meningitis More common in children and affects the pia-arachnoid, its blood vessels and the superficial layer of the brain. It is due to blood spread of a tuberculous focus in the body. It is one of the causes of arachinoid fibrosis which may produce hydrocephalus.

12. Pathological features: A yellowish exudate covers the surface of the brain and is marked over the base. The exudate is composed of fibrin, epithelioid cells, lymphocytes, scanty giant cells and shows areas of caseation. Healing by fibrosis may obstruct the roof of the fourth ventricle causing hydrocephalus. The meninges covering the spinal cord particularly in the cervical region show similar changes.

13. Tubercles on the small blood vessels of the brain, choroid plexus and lining of the ventricular cavities. Areas of softening in the cerebral cortex and basal ganglia. This results from tuberculous end arteritis followed by thrombosis.

14. CSF shows: The fluid is clear and a fine web of fibrin forms on the surface on standing. Moderate increase in mononuclear cells, mainly lymphocytes. Protein level is elevated. Glucose content is moderately reduced or normal. Small number of bacilli could be detected in smears.

15. Complications: Increased intracranial tension. Compression of the cranial nerves leading to their paralysis. Hydrocephalus. May result in well circumscribed mass in the brain substance itself called tuberculoma. Miliary tuberculosis.

16. Septic meningitis

17. Brain Abscess Etiology: Causative organisms: Staphylococcus aureus, streptococcus, pneumococcus, E.coli and bacillus pyocyaneus.

18. Routes of infections: • Direct spread of infection from otitis media, sinusitis and mastoiditis. • Blood spread of infection from acute bacterial endocarditis, bronchiectasis, lung abscess or empyema through the vertebral system of veins. • Infection from outside through compound fractures of the skull.

19. Sites: • The site of the abscess depends upon the primary site from which the infection comes. • Otitis media causes temporal or parietal lobe abscess. • Mastoiditis causes a cerebellar abscess. • Sinusitis, lung infection and fracture causes frontal lobe abscess. • Hematogenous abscesses from system pyemia are multiple and found at the junction of the grey and white matter.

20. Pathological Features: Early the brain tissue shows edema, softening and heavy neutrophilic infiltration. The active liquifactive necrosis is surrounded by zone of congestion. Then an abscess cavity filled with pus and lined by necrotic tissue develops. The affected part appears swollen, the convolutions flattened and the meninges thick and adherent. The abscess tends to spread inwards and rupture into the ventricles.

21. If pus is absorbed or evacuated spontaneous healing occurs by gliosis, but more commonly the abscess changes to chronic one. Chronic abscess is surrounded by a thick wall of reactive gliosis and its inner lining is smooth.

22. Clinically: Progressive focal deficits. Increases ICT and progressive herniation which may be fatal. The CSF white cell count is raised. The CSF protein level is raised. The CSF glucose content is normal. Rupture of abscess can lead to ventriculitis, meningitis, and venous sinus thrombosis.

23. Complications: • Increased intracranial tension and brain herniation. • Septic meningitis, subdural abscess, extradural abscess and sinus thrombophlebitis.

24. Encephalitis Encephalitis means inflammation of the brain and is caused by: Pyogenic infections as brain abscess. Bacterial toxins as botulism. Fungus infections as cryptococcosis. Parasitic infections as malaria and toxoplasmosis. Viral infections as rabies, poliomyelitis, herpes zoster and herpes simplex.

25. Viral encephalitis That is infection of the brain that is invariably associated with inflammation of the meninges (meningio-encephalitis). The most characteristic features are perivascular and parenchymal mononuclear cell infiltrate, microglial nodules and neuronphagia. Certain viruses may form inclusion bodies.

26. VIRAL DISEASES OF NERVOUS SYSTEM • POLIOMYELITIS • Common acute viral infection of the nervous system. • Usually affects infants and young children, but may occur in adults. • It appears either in a sporadic or epidemic form.

27. Etiology: • The virus has three strains. • Infection is transmitted by ingestion of the virus in contaminated food or drink. • Flies transmit the virus from stools of patient or a carrier. • The virus multiply in the intestine, enters the blood stream (viremia), then invades the grey matter of the anterior horn cells of the spinal cord and rarely the brain (brain stem, cerebellum, thalamus and hypothalamus).

28. Pathological Features: • The spinal cord shows swelling of the lumbar and cervical regions. • The affected regions show congestion, petechial hemorrhage and small areas of softening. • Microscopically: • The motor cells of the anterior horn show degeneration and intranuclear inclusions. • The inflamed area shows perivascular cellular infiltrate of lymphocytes and plasma cells.

29. In the healing stage the destroyed cells are removed by the microglia cells and gliosis occurs. • The peripheral nerve fibers related to the affected nerve cells show demyelination and fragmentation of the axis cylinders. • The corresponding muscles become paralyzed and show loss of striations, hyaline degeneration and necrosis of their fibers. • The atrophic fibers are replaced by fibrous or fatty tissue. • Generalized enlargement of the lymph nodes and spleen.

30. Clinically: Prodromal stage:Pyrexia, malaise, headache, nausea, vomiting, and sore throat. Pre-paralytic stage: Pyrexia, neck stiffness, limb and back pain, and signs of meningeal irritation. Paralytic stage: Flaccid paralysis of the muscles supplied by the affected nerve cell.

31. RABIES: • Rare viral disease of the nervous system. • Infection is acquired by bite of a rabid dog or cat. • The virus is present in the saliva of the animal and is introduced into the wound of the bite, from which it reaches the central nervous system along the peripheral nerves.

32. Pathological Features: • The virus invades nerve cells of brain stem, posterior horn of the spinal cord and posterior root ganglia. • Nerve cells show inlracytoplasmiceosinophilic inclusion bodies "Negri bodies" which are virus aggregates in hippocampal pyramidal cells and Purkinje cells. • Affected cells undergo degeneration and necrosis. • Perivascular infiltrations of lymphocytes, plasma cells and neutrophils.

33. Clinically: The patient suffers from spasm of the muscles of deglutition, hydrophopia, with inability of swallowing, Causes extraordinary CNS excitability, convulsions, flaccid paralysis, coma and death.

34. HERPES ZOSTER • Virus infection of the posterior root ganglia characterized by severe continuous pain followed by a rash over the cutaneous distribution of the affected nerve. • The causative virus is related to that of chickenpox and infection is acquired by direct contact.

35. Pathological Features: • Inflammation and degeneration of posterior root ganglia of one or more spinal nerve. • Sometimes cranial nerves, spinal cord or the brain are affected. • Skin lesion in the form of clusters of vesicles on the face or the trunk related to the course of the affected sensory nerve. • The vesicles dry up, become encrusted and disappear in 1-3 weeks.

36. Demyelinating diseases Diseases characterized by damage to myelin with relative preservation of the axons. Multiple sclerosis (MS): An autoimmune disease due to combination of environmental and genetic factors resulting in loss of tolerance to self proteins (myelin antigens). A transmissible agent (virus) has been proposed but not yet identified.

37. Genetic lineage of MS susceptibility to HLA-DR-2 is established. Grossly: Characterized by presence of plaques of demyelination of the white matter. These plaques are perivenular and appear as irregular well demarcated grey or translucent lesions with a diameter ranging between 0.1cm to several centimeters.

38. Sites of predilection are; optic nerve, paraventricular, brain stem, spinal cord, and cerebral white matter. Any area of the brain can be affected. Microscopic: Plaques show demyelination and tangled masses of preserved axons. Lymphocytic infiltration is present in areas of recent demyelination.

39. Clinically: Characterized by episodic relapses and remissions over many years. The clinical manifestations depend on the area of brain affected and include abnormalities of vision, cerebellar dysfunction, parasthesia, weakness and spinal cord dysfunctions.

40. Degenerating diseases Alzheimer’s disease: Principle clinical manifestation is dementia. Usually begins after the age of 50 years. Gyri are narrowed and sulci widened specially in frontal, temporal and parietal lobes.

41. Microscopic: Neurofibrillary tangles; bundles of argrophilic paired helical filaments in neuronal cytoplasm. Neuritic plague. Amyloidangiopathy.

42. Parkinsonism: A disease characterized by tremor, rigidity, bradykinesia and instability. Parkinsonian syndrome: Occurs with diseases, drugs, or toxins that selectively injure dopaminergic neurons in the substanianigra.

43. Pathogenesis of Parkinsonism: Most cases are sporadic, both autosomal dominant and recessive forms do exist. There is defect in α-synuclein, a protein involved in synaptic transmission. Lewy body: an inclusion containing α-synuclein.

44. Grossly: Pallor of the substantianigra and locus ceruleus. Microscopic: Depigmentedsubstantianigra. Lewy bodies appear as single or multiple intracytoplasmic, eosinophilic, round to elongated in lusions with dense core surrounded by a pale halo.

45. Clinical features: Commonly manifests as movement disorder. Progresses producing severe motor slowing over 10-15years. Death usually is the result of inter current infection or trauma from frequent falls caused by postural instability. Dementia (Lewy body dementia) arises within one year of the onset of motor symptoms.

46. CEREBRAL EDEMA

47. Cerebral edema Cerebral edema: It is excess accumulation of fluid in the intracellular or extracellular spaces of the brain, or It is an accumulation of excess fluid within the brain parenchyma. Pathogenesis: Two underlying mechanisms that may occur together in cases of generalized injury:

48. Vasogenic edema: • Occurs when the integrity of the normal brain barrier is disturbed with subsequent increase in the vascular permeability. • Can be either localized adjacent to inflammation or tumors or generalized. • Cytotoxic edema: • An increase in intra-cellular fluid secondary to neural, glial, or endothelial cell membrane injury e.g., generalized, hypoxic/ischemic insult, or with exposure to some toxins.

49. Gross: The edematous brain is softer, and appears to overfill the cranial vault. The gyri are flattened as a result of compression of the expanding brain by the dura matter and the inner surface of the skull. The intervening sulci are narrowed. The ventricular cavities are compressed.

50. VASCULAR DISEASES OF NERVOUS SYSTEM