1. CNS Patology - III Motor Neuron Diseases Jaroslava Dušková Inst. Pathol. 1st. Med. Fac. https://www1.lf1.cuni.cz/~jdusk/Charles University, Prague Intracranial Tumors

2. Neurodegenerative Diseases genetic abnormality modified protein pathologic structures loss of neurons

3. Neurodegenerative Diseases I. Polyglutamine diseases (multiple Cytosin– Adenin–Guanin CAG complexes) m. Huntington II.  – pathies,  –synucleinopathies m. Alzheimeri, m. Parkinsoni (Lewy bodies)

4. Motor Neuron Diseases Axonopathies v toxic v toxoinfectious v metabolic (drugs!) v avitaminoses v traumatic v malignancy associted

5. Motor Neuron Diseases Neuronopathies v Poliomyelitis anterior acuta v Poliomyelitis anterior chronica v Sclerosis amyotrophica lateralis ALS v Paralysis progressiva bulbaris

6. Motor Neuron Diseases 1. paralysis spastica spinalis 2. paralysis progressiva bulbaris C m. Aran Duchenne T (poliomyelitis ant. chronica) m. Werdnig Hoffmann L myatonia congenita Oppenheim 1. + 2. ALS 1. 2.

7. Amyotrophic Lateral Sclerosis Def. motor neuron disease affecting both 1 st and 2 nd neuron of pyramidal tract

8. Amyotrophic Lateral Sclerosis Clinical features v start: 10 – 60 yrs v palsies spastic/ feeble v neurogenous hand muscle atrophy „simian hand“ v bulbar disturbances v death in several years (aspir. bpn.)

9. Amyotrophic Lateral Sclerosis Morphology macro: micro: v atrophy of gyrus praecentralis v atrophy of ventral roots v atrophy of muscles („simian“ hand) v loss of neurons (GPC, ant. horns) v funicular demyelinisation v atrophy (denervation type)

10. Paralysis progressiva bulbaris Clinical features fonation and deglution disturbances tachycardia, dyspnoe (insuff. n. X) Morphology neuronal atrophia nn. IX, X, XI, XII. chewing muscles, tongue Prognosis fatal

11. Case Report ALS man 52 yrs (driver) *1943 †1999 July 1991 physical exercise (mountain bike trip) first symptoms Disturbance of v pronounciation transient, later standing expressive aphasia v swallowing v central hemiparesis dx., later sin. Progression during 4 years death from bronchopneumonia

12. Amyotrophic Lateral Sclerosis Etiopathogenesis (?) v autoimmune v genetic factors (9, 18, 21…) v excitotoxic damage (glutamate release inhibitors prolong the survival)

13. Hypothesis: A motor neuron toxin produced by a clostridial species residing in gut causes ALS. Longstreth WT Jr, Meschke JS, Davidson SK, Smoot LM, Smoot JC, Koepsell TD. University of Washington, Seattle, Washington, USA. Med Hypotheses. 2005;64(6):1153-1156. A yet-to-be-identified motor neuron toxin produced by a clostridial species causes sporadic amyotrophic lateral sclerosis (ALS) in susceptible individuals. Undetected it resides in the gut and chronically produces a toxin that targets the motor system, like the tetanus and botulinum toxins. Some of the toxin would cross to neighboring cells and to the upper motor neuron and similarly destroy these motor neurons. Weakness would relentlessly progress until not enough motor neurons remained to sustain life. If this hypothesis were correct, treatment with appropriate antibiotics or antitoxins might slow or halt progression of disease, and immunization might prevent disease.

14. CNS neoplasms u primary CNS neo: –approx. 2% of all cancers –approx. 20% of cancers in children under 15 u secondary –more frequented than the primary

15. CNS neoplasms - manifestation u epilepsy u focal deficits –palsies u raised intracranial pressure –headache –vomiting –clouding of consciousness, coma –papiledema u hydrocephalus

16. WHO Histological Typing of Tumours of the CNS (1) I. NEUROEPITHELIAL TISSUE T. II. NERVE SHEATH CELLS T. III. MENINGEAL & RELATED TISSUES T. IV. PRIMARY LYMPHOMAS V. T. OF BLOOD VESSEL ORIGIN VI. GERM CELL T.

17. VII. MALFORMATIVE and T.-LIKE LESIONS VIII. VASCULAR MALFORMATIONS IX. ANTERIOR PITUITARY T. X. LOCAL EXTENSIONS of REGIONAL T. XI. METASTATIC XII. UNCLASSIFIED WHO Histological Typing of Tumours of the CNS (2)

18. WHO Histological Typing of Tumours of the CNS III. TUMORs of MENINGEAL and RELATED TISSUES –meningioma –meningeal sarcoma –xantomatous tumours –melanoma (prim.meningeal) –melanomatosis

19. Topic frequency of meningeoma convexity 85 61 parasagital fossa cerebri ant media post 24 os sphenoides medulla other multiple falx n. olfactorius sella n. opticus tentorium 45 27 35 19 12 33 2 14 8 15 30

20. WHO Histological Typing of Tumours of the CNS I. NEUROEPITHELIAL –astrocytic –oligodendendroglial –ependymal, choroid plexus –pineal cell –neuronal –poorly differentiated, embryonal

21. Astrocytoma juvenile – (spongioblastoma polare)

22. Glioblastoma multiforme

23. WHO Histological Typing of Tumours of the CNS I. NEUROEPITHELIAL –astrocytic –oligodendendroglial –ependymal, choroid plexus –pineal cell –neuronal –poorly differentiated, embryonal

24. Ependymoma

25. WHO Histological Typing of Tumours of the CNS I. NEUROEPITHELIAL –astrocytic –oligodendendroglial –ependymal, choroid plexus –pineal cell –neuronal –poorly differentiated, embryonal

26. WHO Histological Typing of Tumours of the CNS I. NEUROEPITHELIAL –astrocytic –oligodendendroglial –ependymal, choroid plexus –pineal cell –neuronal –poorly differentiated, embryonal

27. Medulloblastoma

28. WHO Histological Typing of Tumours of the CNS II. NERVE SHEATH CELLS TUMOURS – neurilemmoma – neurogenous sarcoma – neurofibroma – neurofibrosarcoma

29. WHO Histological Typing of Tumours of the CNS IV. PRIMARY LYMPHOMAS V. VASCULAR TUMOURS –hemangioblastoma –hemangiosarcoma

30. WHO Histological Typing of Tumours of the CNS VI. GERMINAL TUMOURS –germinoma – embryonal carcinoma – choriocarcinoma – teratoma

31. WHO Histological Typing of Tumours of the CNS VII. DYSONTOGENETIC TUMOURS and T. LIKE LESIONS –craniopharyngeoma –Rathke´s cyst –epidermoid cyst –dermoid cyst –colloid cyst of 3rd ventricle –enterogenous cyst, pituicytoma, nasal glioma

32. WHO Histological Typing of Tumours of the CNS VIII. VASCULAR MALFORMATIONS –capillary teleangiectasia –cavernous hemangioma –a.– v. malformation –venous malformation –Sturge Weber (cerebrofacial / trigeminal angiomatosis)

33. WHO Histological Typing of Tumours of the CNS IX. PITUITARY TUMOURS –adenomas –carcinomas X. LOCAL TUMOURS EXTENSIONS –glomus jug. tumour –chordoma –chondroma – chondrosarcoma –esthesioneuroblastoma – cylindroma

34. WHO Histological Typing of Tumours of the CNS XI. METASTATIC TUMORS mostly carcinomas !!! XII. UNCLASSIFIED