Chapter 14 Diseases of the Nervous System 南通大学基础医学院 Chen li

1. Chapter 14 Diseases of the Nervous System 南通大学基础医学院 Chen li

2. The specificness of diseases of the nervous system: • 1 The localization of function in the CNS, which has four major consequences: • (1) The brain is vulnerable to small focal lesions that would be asymptomatic in other organs. • (2) The same pathologic process manifests in a different way when it affects a different part of the system，e.g. meningioma :in thefactory groove ---anosmia，at the foramen magnum ---progressive quadriparesis. • (3) There are regions of selective vulnerability to particular pathologic • insults, e.g., Purkinje cells of the cerebellum and pyramidal neurons • of the hippocampus are particularly vulnerable to ischemia. • (4) The same type of pathologic change can occur in different diseases (e.g., neurofibrillary tangles). Diagonosis is by distribution (localization) of the pathologic change. • 2 The nervous system has specific anatomic and physiologic features that affect the expression of disease, principally the presence of the skull, the CSF, the blood-brain barrier, and the absence of lymphatic drainage. • 3 Diseases of the nervous system fall into two main groups: • Those that occur in both the nervous system and other organs , e.g., • ininfections. • (2) Conditions unique to the nervous system, notably the diseases of myelin • and system degenerations of neurons.

3. Section 1 Infectious diseases ① those of the meninges and CSF ------meningitis ②those of the brain parenchyma ------encephalitis ③meningitis extends into the brain or encephalitis spills over into the CSF-----Meningoencephalitis

4. Bacterial infection-----Epidemic cerebrospinal meningitis Viral infection------Epidemic encephalitis B ------ Poliomyelitis ------Spongiform Encephalopathies

5. 一、Epidemic cerebrospinal meningitis It is an acute purulent inflammation of meninges which was caused by meningococcus . Epidemic cerebrospinal meningitis is the most frequent pyogenic infection of the nervous system. It may occur at any age but is most common in children.

6. （一）Etiology and pathogenesis Etiology The most cause was :meningococci, pneumococci, streptococci, and hemophilus. The second was：Staphylococci and gram-negative bacteria Pathogenesis microorganisms infected sinus meninges meningitis or ear septicemia breakthrough the blood brain barrier Meningina ;arachnoid 2%-3%

7. （二）Clinical features （exclude fever and other systemic infection symptoms） The main symptom of nervous system： 1、increased intracranial pressure （inflammation、hydropsia): intense headache, projectile vomiting,infant bregmatic space projectile 2、the symptom of meningismus： stiffneck defend spasmus and limitation of movement infant opisthotonus positive of kernig 3、the symptom response to cranial nerve palsy（Ⅲ、Ⅳ、Ⅴ、 Ⅵ、Ⅶ pair) 4、the variation of CSF ：cloudy 、increased pressure、as many as 90,000 neutrophils/mm3 , a raised protein level, a reduced glucose content, bacteria may be seen on a smear .

8. （三）Pathology Grossly A varying amount of exudates is seen in the subarachnoid space overlying the base of the brain and spinal cord. Exudates distribute along the blood vessel, yellow.The structer of cortical sulci and cerebral convolution are not clear.

9. Microscopical 1、 The subarachnoid space contains pus(many pus cells+Lc and Mc+diplococcus） 2、The exudates confined to the leptomeninges. The underlying brain and cord are edematous and congested. 3、In fulminant meningitis, inflammatory cells infiltrate and produce a venulitis that may lead to venous occlusions and infarctions.

10. （四）Prognosis Recovery with complete resolution is common motality is less than 5% to 10%. （五）Complications If a low-grade infection persists, trabeculae form across the subarachnoid space, follow by progressive fibrosis, with narrowing or localized obliteration of the subarachnoid space. When such changes are localized to basilar leptomeninges near the foramina, the outflow of CSF from the ventricular system is blocked, leading to hydrocephalus. The symptoms response to cranial nerve palsy：Permanent disabilities include facial paralysis, deafness, strabilismus, speech defect,or mental deficiency.

11. Fulminant Neisseria intracellularis septicemia（addition） It is a type of fulminant cerebrospinal meningitis .And it most common in children. The onset is usually sudden. Patient's condition is dangerous,and often die in short term. Clinical feature peripheral circulatory failure shock skinPurpura Pathology Waterhouse-Friederichsen syndrome pathological changes of meninges is light Waterhouse-Friederichsen syndrome fingers two sides adrenal gland severity bleeding in severity septemia ,and adrenal cortex nonfuction.It often occurs in fulminant Neisseria intracellularis septicemia Pathogenesis releasing of endotoxin inducetoxic shock and DIC.

12. Fulminant meningocerebritis Pathology meningitis brain tissue beneathmeningina: brain tissue congestion Severity brain edema Clinical sudden increase of intracranial pressure outbreak ardent fever severe headache frequent vomitus eclampsia、comaor cerebral hernia

13. 二、Viral infections （一）Pathogenesis When infection of the brain parenchyma is termed, encephalitis and viruses involve the CNS, they invade both neural and meningeal areas, producing a meningoencephalitis route of transmission： via an insect bite （equine encephalitis ）， by the gastrointestinal route (poliomyelitis) ， via the skin or mucosa (herpes) ， it may reach the CNS via the peripheral nerves （rabies）or by hematogenous spread.

14. （二）Pathology 1 neuron degeneration gliosis ； perivascular inflammatory response (chiefy in mononuclear cells ) .

15. 2 Inclusion bodies are seen in neural and glial cells in some infections These bodies may be nuclear (herpes) or cytoplasmic(rabies). The characteristic Negri bodies seen in rabies are eosinophilic, oval to bullet-shaped, intracytoplasmic inclusions found only in neurons.

16. Viral tropism is particularly striking in the nervous system; e.g., poliomyelitis affects anterior horn motor neurons. Latency is also important, particularly with herpes simplex and varicellazoster. Slow virus diseases have both a long latent period and a slow progression. • 3 Other virus-associated effects : • An immune-mediated perivenous encephalitis; • Reye’s syndrome; • Congenital malformations; • Post encephalitis Parkinson’s disease(post viral influenza).

17. （三） Major tpyes 1、Epidemic encephalitis B 2、Poliomyelitis 3、Spongiform Encephalopathies

18. 1、Epidemic encephalitis B （一）Etiology Etiology infection of arthropod-borne viruses . Most cases of arbovirus encephalitides occur in late summer. Vectors mosquitoes long-term long-term long-term(cow,horse,pig) Infection sources silent infection of patients , cow,horse and pig

19. （二）Morphology Grossly： Brain Substance swelling、congestion 、edema

20. microscopically ： • Nonspecific perivascular inflammation ,(perivascular cuffing) • Glialcell proliferation become microglial nodules, which are sometimes most pronounced in the brain stem are seen. • Neuron degeneration necrosis ： Satellitosis neuronophagia Focal parenchymal soften with necrosis inflammatory cells infiltration.

21. ① Satellitosis : neuron undergo degeneration and surround at least five proliferative oligodendroglial cells,which from satellitoid structure. ② neuronophagia: the process is that neuron is phagacyted by proliferative small glial cells or macrophages.

22. ③ form of focal parenchymal soften Definition focal necrosis and liquation ofnervous tissues,which formed puff texture、dilute stain grit focus of infection.

23. （三）Clinical features 1、seizures, confusion or coma:the most early and main symptoms 2、sometimes with headache, vomit intracranial hypertension and herniation, Cerebellar tonsillar hernia can cause sudden breathing stop and death by press the medullary respiratory center.

24. 2、 Poliomyelitis Etiology ： Poliomyelitis is caused by poliovirus, a small RNA virus that is transmitted gastrointestinally by sewage-contaminated water. The virus is neurotropic, chiefly affecting the spinal cord and brain stem. Clinical features ： Patients may or may not manifest gastrointestinally symptoms; but within a few weeks of infection, they show lower motor neuron paralysis, usually affect the lower limbs. The brain stem neurons may become affected, and the resultant respiratory paralysis may be fatal. Surviving patients have significant neurologic sequelae, especially affecting the legs. Clinically, loss of lower motor neurons produces a permanent flaccid paralysis with muscle wasting and hyporeflexia in the affected spinal segments.

25. Pathology Grossly ： the spinal cord may show small hemorrhages and congestion. Microscopically The anterior horn cells of the cord are affected predominantly neutrophilic infiltration gliosis marrow intumescentia lumbalis is predominantly. more up more lessen atrophy of the anterior (motor) spinal roots, and neurogenic atrophy of the denervated muscle.

26. 3、 Spongiform Encephalopathies The spongiform encephalopathies represent a group of diseases that includes Creutzfeldt-Jacob disease(CJD) and a number of other exceedingly rare conditions(kuru; Gerstomann-Straussler syndrome and fatal familial insomnia; and, in some animals, scrapie and “mad cow” disease). These diseases are transmitted by a unique category of proteinaceous infectious particles termed prions that lack DNA or RNA. Infectious prions are a modified form of a normal structural protein found in the mammalian nervous system. The major difference between normal prion proteins and pathogenic prions is in their conformation. Apparently, the pathogenic prions propagate themselves by contacting their normal counterparts and inducing them to refold in the pathogenic conformations. As this cycle continues, an ever-increasing population of normal prion proteins is converted into the disease-causing form. Because they lack nucleic acids, prions are remarkably resistant to many agents that normally inactivate viruses, such as ultraviolet light and standard disinfectants.

27. CJD is probably the best characterized of the human spongiform encephalopathies. Both sporadic and familial cases of CJD occur, and rare instances of iatrogenic transmission have occurred in patients who have received corneal transplants and human pituitary extract. In the early stages of CJD, the brain is grossly normal. Atrophy is present in cases of long duration and may be severe. The hallmark of CJD and other spongiform encephalopathies is the presence of vacuoles within neuropil and cell bodies in gray matter (spongiform change). The vacuolation is accompanied by a variable degree of neuronal loss and reactive gliosis, the degree of which increases with the duration of the disease. Inflammatory infiltrates are usually absent. CJD is characterized by rapidly progressive dementia, often accompanied by gait abnormalities and startle myoclonus. The disease is invariably fatal, with most patients succumbing within about a year after the onset of symptoms.

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