CNS II morphology of dementia by mikeholy

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									                  CNS Pathology - II

Pathology
    of
 Dementia
Jaroslava Dušková


Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague
Dementia
Def.
           decrease of individual
   intelectual abilities under the
        formerly reached niveau
Dementia
Clinical features
 Disturbances of
    memory              (mnestic)
    cognitive functions (gnostic)
    adaptative behaviour (practice)
Dementia
Beginning
            mostly inapparent
Course
            reversible
            stationary
            progredient
Dementia - causes (1)
   THERAPY       MALNUTRITION

   INTOXICATION  VASCULAR
   INFECTION      EXPANSION
   METABOLIC  AFFECTIVE
     DISORDERS        DISORDERS
   PROGRESSIVE DEGENERATIVE
                     DISEASES
Dementia - causes (2)
    THERAPY                 polypragmasia
    INTOXICATION            Mn, Cu, Pb,
                    CO, CS2, Hg, etanol…..

    INFECTION                   viral, bacterial
                           protozoan, mycotic
    (HIV, PME, Whipple disease, Lues,
     toxoplasmosis, cryptococcosis, prion dis.)
Prionoses
              - morphology
   neuronal loss
   spongiosis
   gliosis         ATROPHY
Dementia - causes (3)
       METABOLIC DISORDERS
            chron. liver or kidney failure,
            thesaurismoses
            hepatolenticular degeneration
       MALNUTRITION
       avitaminosis B1
       Wernicke-Korsakoff encephalopathy
                            with dementia
  Storage Diseases
Def.:
    inborn errors of metabolism (mostly
     single gene abnormality) leading to an
    enzyme defect with subsequent

    accumulation of the substrate (&

    lack of the product) in tissues or

     organs
  Lipid Storage Diseases -1.
Disease    E- def     Accum.        Tissues
                      Lipid         Involved
Tay-Sachs Hexos       GM2           Brain,
          aminidase A ganglioside   retina
Gaucher   -          Gluco         Liver, spleen,
          Glucosidase cerebrosid    bone marrow,
                                    brain
Niemann-   Sphingo     Sphingo      Brain, liver
Pick       myelinase   myelin       spleen
  Lipid Storage Diseases – 2.
Disease     E- def         Accum.       Tissues
                           Lipid        Involved
Metachro    Arylsulfat     Sulfatid     Brain, kidney,
matic       ase A                       liver, peripheral
Leuco                                   nerves
dystrophy
Fabry´s     -galactosid   Ceramid      Skin, kidney
            ase            trihexosid
Krabbe´s    Galactosyl     Galactol    Brain
            ceramidase     cerebroside
  Mucopolysaccharidoses
Disease,    E- def         Accum.       Tissues
inheritance                Mucopoly     Involved
course                     saccharide
Hurler      -l-           Heparan      Skin, cornea,
            iduronidase    sulfate,     bone heart,
AR, severe                 dermatan     Brain, liver
                           sulfate      spleen
Hunter       l-            Heparan      Skin, bone,
X, rec.      iduronosulf   sulfate,     heart, ear,
moderate     ate           dermatan     retina
             sulfatase     sulfate
Sanfilippo   Many types    Heparan      Brain, skin
                           sulfate
Dementia – causes (4)
   VASCULAR
       hypertensive encephalopathy,
                              MID
   EXPANSION
       subdural hematoma, hygroma,
       neoplasia, hydrocephalus
   AFFECTIVE DISORDERS
       depression
Dementia - causes (5)
PROGRESSIVE DEGENERATIVE
                        DISEASES
 dementia – the only one symptome:
         m. Alzheimer, m. Pick

   dementia – combined with neurology
                             symptomes:
     m. Parkinson, m. Huntington, ALS, PP
M. Alzheimeri - incidence

 65 yrs       5%
            population
 80 yrs       20%
M. Alzheimeri
Extracellular
 -amyloid plaques
 dystrophic dendrites
 axons
 activated microglia
 reactive astrocytes
diffuse plaques - A42
mature plaques - A42
   and
      A40
M. Alzheimeri
            Intracellular
             neurofibrillary  deposits
                hyperphosphorylated
                proteins (pair helical
                filaments)
                 glycosaminoglycans
                 admixture (heparin)
  M. Alzheimeri- genetic factors
Chromo      Gene defekt      Age          A phenotype
 -some                     of onset

  21      APP mutations     50s      Production of total A 42
                                            peptides
  19     apo E4            60and      Density of Aplaques
         polymorphism      older      and vascular deposits
  14     presenilin 1      40s and      Production of A 42
         mutations           50s            peptides
  1      presenilin 2        50s        Production of A 42
         mutations                          peptides
M. Alzheimeri - diagnosis
age matched
       neuritic plaques
                quantity
   Khachaturyan, Mirra et al.
Dementia - causes (5)
PROGRESSIVE DEGENERATIVE
                        DISEASES
 dementia – the only one symptome:
         m. Alzheimer, m. Pick

   dementia – combined with neurology
                             symptomes:
     m. Parkinson, m. Huntington, ALS, PP
Arnold Pick 1851-1924

                Head of the Prague
                Psychiatry Clinic 1886-1924



                Prager medizinische
                Wochenschrift 1882 – case
                report of a dementia patient



                         Pick disease
Dementia - causes (5)
PROGRESSIVE DEGENERATIVE
                        DISEASES
 dementia – the only one symptome:
         m. Alzheimer, m. Pick

   dementia – combined with neurology
                             symptomes:
     m. Parkinson, m. Huntington, ALS, PP
    Paralysis agitans
                          – m. Parkinsoni (1817)
Clinical features
    Start 40–60 years
    Early stage
         dysesthesias
         discrete   tremor
   hypertonia–hypokinesis syndrome
         resting tremor
         rigidity
         bradykinesia & loss of automatic movements
       prognosis: quoad vitam good,
        quoad sanationem  (L-DOPA, transpl., nicotine)
Paralysis agitans
      – m. Parkinsoni (1817)
Morphology
    macroscopy         depigmentation of
           substantia nigra mesencephali
    microscopy      Lewy bodies ,
                  loss of pigmented neurons
    Parkinson´s dis. - etiology
   genetic factors recently described:
    – PARK1 – α-synuclein- autos. dom., Lewy bodies
    – PARK2 – Parkin, autos. rec. juv.-no LB
    – PARK3 –late onset
    – …..
    – …..
    – PARK 11 …
Causes of Parkinsonism
   common
    – Parkinson´s dis.
   less common
    –   drug induced
    –   multiple system atrophy
    –   progressive supranuclear palsy
    –   vascular
 rare
    – Alzheimer´s dis., Huntington´s dis., Wilson´s dis.,
      toxins, dementia pugilistica, hydrocephalus, space
      ocupying lesions….
    Chorea chronica
    progressiva Huntington
   Autosomally dominant (!)
                       4th chromosome
    Manifestation 25 – 45 years
        (juvenile form prior to 20 years of age)

    Duration 15 years
Chorea chronica progressiva
Huntington
Clinical features
     contravolitional uncontrolled
               dance–like motions
     schizophrenic and depressive
               personality features
     death from intercurrent infection
        (bronchpneumonia, cachexia)
 Chorea chronica
 progressiva Huntington
Morphology
    macroscopy striatum atrophy
                (ncl. caudatus + putamen)
    microscopy loss of small GABA
          neurons (norm. 80% of
     population)
Neurodegenerative Diseases
  genetic abnormality

  modified protein

   pathologic structures

   loss of neurons
 Neurodegenerative Diseases
I. Polyglutamine diseases
   (multiple Cytosin– Adenin–Guanin CAG
                               complexes)
                            m. Huntington
  (+ family of other triplet repeat expansion dis.)

II. – pathies,  –synucleinopathies
   m. Alzheimeri, m. Parkinsoni (Lewy bodies)
Sclerosis cerebrospinalis
multiplex disseminata MS
Def.
        chronic autoimmune
 disease with myelin breakdown
    Multiple sclerosis – classif.
    classic (Charcot type)
    acute (Marburg type)
    neuromyelitis optica (Devic´s
                                   dis.)
   concentric sclerosis (Baló ´s dis.)
Sclerosis cerebrospinalis
multiplex disseminata MS
Clinical features
Disorders of           sight
                       sensation
                       motorics

                       cont. progressive
Course                 saw-like
Sclerosis cerebrospinalis
multiplex disseminata MS
Morphological features
 – myelinic plaques
    acute
    chronic
Sclerosis cerebrospinalis
multiplex disseminata MS
Pathogenesis
 genetic predisposition
 viruses
MS – viral influence (morbilli,
                               herpes,…)
Pathogenesis
 interaction macroorganism x virus
  limited production of Ig (only 10-20%
              produced viruses are virulent)
   virus mutation & immunosuppression
      (age, pregnancy, stress, other disease)
MS – viral influence          (2)

Pathogenesis
 infection of endothelia – microangiitis
 hematoencephalic barier disorder
 serum and CSF        CD4,      CD8

                  (mirror image to AIDS)

								
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