cns patology - iii

CNS Patology - III

Motor Neuron Diseases

Jaroslava Dušková Inst. Pathol. 1st. Med. Fac. https://www1.lf1.cuni.cz/~jdusk/ Charles University, Prague

Intracranial Tumors

Neurodegenerative Diseases

genetic abnormality

modified protein

pathologic structures

loss of neurons

Neurodegenerative Diseases

I. Polyglutamine diseases (multiple Cytosin– Adenin–Guanin CAG

complexes)

m. Huntington

II. – pathies, –synucleinopathies m. Alzheimeri, m. Parkinsoni (Lewy bodies)

Motor Neuron Diseases

Axonopathies toxic toxoinfectious metabolic (drugs!) avitaminoses traumatic malignancy associted

Motor Neuron Diseases

Neuronopathies Poliomyelitis anterior acuta Poliomyelitis anterior chronica Sclerosis amyotrophica lateralis ALS Paralysis progressiva bulbaris

Motor Neuron Diseases1. paralysis spastica spinalis 2. paralysis progressiva bulbaris C

m. Aran Duchenne T (poliomyelitis ant. chronica)

m. Werdnig Hoffmann L myatonia congenita Oppenheim1. + 2. ALS

Classification of Disorders Affecting Motor Neurons

Primary– idiopathic (ALS)– inherited (SMA)

Secondary– infective :acute poliomyelitis, HIV, syphilis, prions– metabolic: hyper/hypo thyr, hyperparathyr…– immune. paraproteinemia– Environmental/toxic: Pb, Sb, Cd…neurolathyrism– vascular– paraneoplastic: nHML, MLH

Multisystem neurodeg. diseases affecting motor neurons– Western Pacific ALS /Parkinson/dementia complex– spinocerebellar deg– Huntington´s disease– prionoses

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.

Amyotrophic Lateral Sclerosis

Def.

motor neuron disease affecting

both 1st and 2nd neuron of pyramidal

tract

Amyotrophic Lateral Sclerosis

Clinical featuresstart: 10 – 60 yrspalsies spastic/ feebleneurogenous hand muscle atrophy

„simian hand“bulbar disturbancesdeath in several years (aspir. bpn.)

Amyotrophic Lateral Sclerosis

Morphologymacro:

micro:

atrophy of gyrus praecentralis

atrophy of ventral roots

atrophy of muscles („simian“ hand)

loss of neurons (GPC, ant. horns)

funicular demyelinisation

atrophy (denervation type)

Paralysis progressiva bulbaris

Clinical featuresfonation and deglution disturbances tachycardia, dyspnoe (insuff. n. X)

Morphology neuronal atrophia nn. IX, X, XI, XII.

chewing muscles, tonguePrognosis fatal

Case Report ALSman 52 yrs (driver) *1943 †1999

July 1991 physical exercise (mountain bike trip)

first symptomsDisturbance of

pronounciation transient , later standing expressive aphasia

swallowing central hemiparesis dx., later sin.

Progression during 4 years death from bronchopneumonia

Amyotrophic Lateral Sclerosis

Etiopathogenesis (?)

autoimmune

genetic factors (9, 18, 21…)

excitotoxic damage (glutamate release

inhibitors prolong the survival)

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.

CNS neoplasms

primary CNS neo:– approx. 2% of all cancers– approx. 20% of cancers in children under 15

secondary– more frequented than the primary

CNS neoplasms - manifestation

epilepsy focal deficits –palsies raised intracranial pressure

– headache– vomiting– clouding of consciousness, coma– papiledema

hydrocephalus

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.

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)

WHO Histological Typing of Tumours of the CNS

III. TUMORs of MENINGEAL and RELATED TISSUES

– meningioma– meningeal sarcoma– xantomatous tumours– melanoma (prim.meningeal)– melanomatosis

WHO Histological Typing of Tumours of the CNS

I. NEUROEPITHELIAL– astrocytic– oligodendendroglial– ependymal, choroid plexus– pineal cell– neuronal– poorly differentiated, embryonal

WHO Histological Typing of Tumours of the CNS

I. NEUROEPITHELIAL– astrocytic– oligodendendroglial– ependymal, choroid plexus– pineal cell– neuronal– poorly differentiated, embryonal

WHO Histological Typing of Tumours of the CNS

II. NERVE SHEATH CELLS TUMOURS

– neurilemmoma

– neurogenous sarcoma

– neurofibroma

– neurofibrosarcoma

WHO Histological Typing of Tumours of the CNS

IV. PRIMARY LYMPHOMAS

V. VASCULAR TUMOURS

– hemangioblastoma

– hemangiosarcoma

WHO Histological Typing of Tumours of the CNS

VI. GERMINAL TUMOURS

– germinoma

– embryonal carcinoma

– choriocarcinoma

– teratoma

WHO Histological Typing of Tumours of the CNSVII. DYSONTOGENETIC TUMOURS

and T. LIKE LESIONS

– craniopharyngeoma– Rathke´s cyst– epidermoid cyst– dermoid cyst– colloid cyst of 3rd ventricle– enterogenous cyst, pituicytoma, nasal glioma

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)

WHO Histological Typing of Tumours of the CNSIX. PITUITARY TUMOURS

– adenomas– carcinomas

X. LOCAL TUMOURS EXTENSIONS– glomus jug. tumour– chordoma– chondroma – chondrosarcoma– esthesioneuroblastoma – cylindroma

WHO Histological Typing of Tumours of the CNS

XI. METASTATIC TUMORS

mostly carcinomas !!!

XII. UNCLASSIFIED