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

7. Classification of Disorders Affecting Motor Neurons u Primary –idiopathic (ALS) –inherited (SMA) u Secondary –infective :acute poliomyelitis, HIV, syphilis, prions –metabolic: hyper/hypo thyr, hyperparathyr… –immune. paraproteinemia –Environmental/toxic: Pb, Sb, Cd…neurolathyrism –vascular –paraneoplastic: nHML, MLH u Multisystem neurodeg. diseases affecting motor neurons –Western Pacific ALS /Parkinson/dementia complex –spinocerebellar deg –Huntington´s disease –prionoses

8. β-ODAP = 3-N-oxalyl-L-2,3diaminopropionic acid The level of this compound in the dry seeds varies depending on genetic factors and environmental conditions.

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

10. 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.)

11. 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)

12. 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

13. 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

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

15. 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.

16. 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

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

18. 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.

19. 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)

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

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

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

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

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

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

26. 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

27. 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)

28. 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

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