3DEMYLEINATING DISEASES Multiple sclerosis (M.S.)_ Definition:Chronic relapsing-remitting (complete or partial recovery then another attack) disorder of an autoimmune originCharacterized by episodes of demylination in the brain, optic nerve and spinal cord resulting in progressive neurological deficits
4Pathology: Acute lesion: Grossly: peri-ventricular well-circumscribed plaquesMicroscopically:Loss of myelinPhagocytosis of myelin by macrophagesPreservation of axonsChronic inflammatory cellsChronic lesion:No inflammationAxon remyleinationBut remyleination is defective
6Pathophysiology: During the acute stage: nerve conduction is blocked Chronic disease: there is slow nerve conductionRecurrent attacks → progressive neurological deficit
7According to the site of nerve demylenation: Clinically:According to the site of nerve demylenation:Vertigo (brain stem involvement)Loss of sensation and movement in a limb (spinal nerves involvement)Neuropsychiatry disorders
11Clinically: Slowing of all voluntary movements Tremors at rest that disappear on movementExpressionless faceRigidity in limbs and trunk and inability to initiate voluntary movementsAssociated with increased incidence of dementia and depression
12Huntington’s disease (HD) Definition:Autosomal dominant disorder characterized by atrophy of caudate nucleus with secondary ventricular dilatation
13Huntington disease (HD) Atrophy of caudate nucleusHuntington disease (HD)
14Microscopically: Clinically: Loss of small neurons in caudate nucleus Age: yearsChorea: sudden, unexpected and purposeless contractions of the proximal musclesChanges in the personality with tendency to suicide and dementia
153- Alzheimer disease: Risk factors: Pathologically: Aging Significant head traumaPathologically:Accumulation of abnormal proteins intra and extra cellularSenile plaques: core of amyloid surrounded by dendretic processes, microglial cells and astrocytes
17Clinically:Gradual onset, usually begins in the seventh or the eighth decadesProgressive memory impairmentAlteration in mood and behaviorProgressive disorientationAphasia (loss of language)Within 5-10 years become mute and bedridden
18CNS infectious disease are classified as: CNS INFECTIONSCNS infectious disease are classified as:Bacterial infectionViral infectionFungal infectionToxoplasmosis infectionPrion infection
22Pathological features: Clinical features:Diffuse cerebral edema with increased risk of brain herniationHeadache, fever, nuchal rigidity, cloudy sensorium, coma and deathHydrocephalus and cranial nerve impairmentPathological features:Neutrophilic infiltration of the meninges and extending to the cortex
23Cerebral abscessHematogenous spread or direct spread from contiguous focciPredisopsing conditions:Acute bacterial endocarditis and chronic pulmonary abscessMastoiditis, paranasal sinusitis, acute otitis, open fractures and previous neurosurgeryClinically:Signs of increased intracranial pressure (headache, vomiting and papilledema)Focal neurological deficits
25Viral infection of CNS Poliomyelitis: Etiology & pathogenesis: It is a viral infection of the nervous system by poliovirus, an entero-virus transmitted by fecal-oral route.The virus enters the body through the intestine and multiplies in lymphoid tissues of oropharynx and intestine (incubation period) then invades the blood stream then it reach the brain and spinal cord.Poliomyelitis is now rare because of routine immunization during childhood
27c- Human Immunodeficiency Virus (HIV): Cerebral involvement with HIV leads to AIDS dementiaHistologically :Microglial nodulesDiagnostic giant cellsSpinal nerve involvement leads to vacuolar myelopathy
28Primary manifestations of AIDS HIV encephalitis: multinucleated giant cells, gliosis and inflammation
29Toxoplasmosis Frequent in AIDS patient Clinically: Cerebral abscess with central necrosis and chronic inflammation
31Prion disease of brain Creutzfedt-Jacob disease: CNS disease caused by prion protein. The infectious agent has been called a prion.A prion is defined as "small proteinaceous infectious particles".Prion diseases are often called spongiform encephalopathies because of the post mortem appearance of the brain with large vacuoles in the cortex and cerebellum.
32Pathological features: Vacuolation of the gray matter in the cortexNeuronal lossKuru plaques: these are deposites of amyloidClinically:These cases rapidly progress to dementia and memory lossInvoluntary movmentsDeath within 6-12 months
33Spongiform encephalopathies cause the brain tissue to become spongy and riddled with microscopic holes.
35CLASSIFICATIONTumors of the CNS can be classified according to five fundamental origins:The neuroectoderm (principally gliomas)Mesenchymal structures (notably meningiomas and schwannomas, and primary brain lymphoma)Tissues and cells that have been ectopically displaced intracranially during embryonic developmentRetained embryonal structuresMetastases
36Astrocytomas The most common type of glioma Accounts for 15-20% of primary brain tumors in the adultThe highly malignant form is called Glioblastoma MultiformeGrossly:The tumor has poorly defined margins and is infiltrative.Most commonly found in cerebral hemispheresMicroscopically:Uniform appearing nuclei occur in fibrillary background or matrix
38Oligodendroglioma Slowly growing tumour Seizures and convulsions are the prominent 1st complaint
39EpendymomaOccurs most commonly in the 4th ventricle and in that location may lead to obstructive hydrocephalus.Ependymoma in 4th ventricle
40Meningiomas “Tumor of the meninges" II- Mesenchymal OriginMeningiomas “Tumor of the meninges"Accounts for 20% of primary adult brain tumorsOccurs in later decades of lifeExtremely slow growing and benignCommon presenting symptoms include headache, seizures and dementia
41Metastatic Tumors Account for 50% of all brain tumors in adults In order of propensity to metastasize: lung, breast, melanoma, kidney, thyroidCarcinomas of the GI tract, bladder, prostate, ovaries and uterus rarely go to brainGrossly, tend to be round with well-defined borders.Necrosis and hemorrhage are frequent.Usually multiple
43SCHWANNOMA (NEUROLEMMOMA) Definition:A bengin tumor arising from Schwann (neurilemma) cells of the peripheral (cranial or spinal) nerves.Gross:A firm grayish capsulated mass at one side of the nerve.The 8th cranial, acoustic nerve is one of the famous sites of schwannoma.
44NEUROFIBROMA Pathology: Appears as rubbery expansion of the affected nerve, not demarcated from nerveNeurofibroma has a significant risk of malignant transformation
45NEUROFIBROMATOSIS (Von Recklinghausen's disease of nerves) It is a familial disease (autosomal dominant inheritance) of two types:Type I (NFI):It is characterized byMultiple neurofibromatosis, mainly cutaneousAcoustic schwannomasCafé au lait spots (hyperpigmented skin macules)Eye lesions:Optic nerve gliomasPigmented nodules of irisType II (NFII):It resembles type I without eye affection
47MALIGNANT SCHWANNOMAAlso called malignant peripheral nerve sheath tumor (MPNST)It is a poorly differentiated spindle cell sarcoma of peripheral nerve.The tumor may arise de novo or from malignant transformation of a neurofibroma or neurofibromatosis.Occus in adults in the larger nerves of the trunk or proximal limbs as an uncapsulated fusiform enlargement of a nerve.
48PERPHERAL NEURITIS Definition: Causes: This is inflammation and degeneration of peripheral nervesCauses:Diabetes mellitus is one of the most common causes of peripheral neuritisChronic alcoholismChronic lead poisoningBeriberi
49LeprosyToxemia as diphtheriaAcute post-infective polyneuritis; it follows infective diseases as measles and influenza or after vaccination and is thought to be allergic natureIschemia as in cases of polyarthritis nodosaTraumatic as in cases of disc prolapse
50Signs and symptomsDeficits which include numbness, tremors and gait abnormality, loss of function, tiredness and heaviness.Symptoms include tingling, pain, itching and pins and needles.Pain can become intense enough to require use of opioid (narcotic) drugs (i.e., morphine).
51Skin can become very hypersensitive Skin can become very hypersensitive. People with this degree of sensitivity cannot have a bed-sheet touch their feet or wear socks or shoes.There is also pain in the muscles (myalgia), cramps.
53LeprosyLeprosy is a chronic slowly progressive, destructive process involving peripheral nerves, skin and mucous membranes.Caused by Mycobacterium leprae.Leprosy is transmitted from person to person usually as a result of years of intimate contact.
54Vitamin B3 deficiency (niacin, nicotinic acid): Pellagra: Clinical niacin deficiency, characterized by dermatitis, diarrhea and dementia, and also glossitis and degeneration of posterior and lateral columns of the spinal cord.
56Vitamin B6 deficiency (pyridoxine): Deficiency is related to the development of neuropathy.
57Folic acid deficiency (Vitamin P): Megaloblastic (macrocytic) anemiaHypersegmented neutrophilsAssociated with neural tube defects in utero
58Vitamin B12 deficiency (cobalamin, cyanocobalamin): Vitamin B12 is present in all foods of animal origin. Deficiency causes ("pernicious anemia").Macrocytic anemia, demyelinized posterior columns ("subacute combined degeneration of the cord"), later brain dysfunction.
60Guillian–Barré syndrome An acute polyneuropathy, a disorder affecting the peripheral nervous systemAscending paralysis, weakness beginning in the feet and hands and migrating towards the trunk.It can cause life-threatening complications, in particular if the breathing muscles are affected
61The disease is usually triggered by an infection. The diagnosis is usually made by nerve conduction studies.With treatment the majority will recover completely.Guillain–Barré syndrome is rare, at 1–2 cases per 100,000 people annually, but is the most common cause of acute non-trauma-related paralysis in the world.Can be confused clinically with poliomyelitis