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About degenerative disease
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DEGENERATIVE DISEASES
Penyakit degeneratif SSP dapat mengenai :1. Substansia abu2. Substansia putih3. Kombinasi
Daerah yang terkena :- Sering kali difus- Biasanya satu area atau sistem lebih dari lainnya
KLASIFIKASI ANATOMIS
KLASIFIKASI ANATOMIS
I. Diseases of the gray matter
II. Hereditary diseases of white matter
III. Neuroectodermal degeneration – phakomatoses
IV. Diseases of mitochondria
V. Disorders of cerebrospinal fluid and circulation
DISEASES OF GRAY MATTER
DISEASES OF THE CEREBRAL CORTEX.
DEMENTIA
- A progressive deterioration of intellectual capacity resulting from diseases of the brain- 80% due to Alzheimer disease and multi-infarct dementia- The third leading of death in old age group- Clinical manifestation :
- Memory impairment (predominant) – and impaired of :- Language- Perception- Visuospatial function - Calculation- Judgment - Abstraction - Problem solving skills
DISEASES OF GRAY MATTER ( lanj’ )
DISEASES OF THE CEREBRAL CORTEX.
DEMENTIA- In Degenerative Disease, the etiologies are unknown, but dementia is a predominant sign- The group of diseases with dementia :
- Alzheimer disease- Pick disease- Multisystem disease- Progressive supranuclear palsy- Huntington disease- Lewy body disease- Cortical basal degeneration- Creutzfeldt-Jacob disease- Fronto-temporal dementia- Normal Pressure Hydrocephalus (NPH)- Vascular dementia
Evaluation of Patients with Dementia1. The history obtained from the patient and other ones
Early cases : punctuated by denial Advanced cases : sparse, fragmented, hesitant
2. The neurological examination MMSE Primitive reflexes Hypertonia or paratonia Dyspraxia Abnormal in reflexes examination
3. The general physical examination Important to exclude signs of: hypoparathyroidism, vascular disease with hypertension, cardiac murmurs,
carotid bruit, Vit B12 deficiency 4. Diagnostic procedures
CAUSES OF TREATABLE DEMENTIA
Therapeutic drug use : - Anticholinergics – atropine and related comp[ounds- Anticonvulsants : phenytoin, mephenytoin, barbiturates- Antihypertensives : clonidine, methyldopa, propanolol- Psychotropics : haloperidol, lithium carbonate, phenothiazine- Miscellaneous : disulfiram, bromides, paraldehyde, quinidine
Metabolic – systemic disorders :Elctrolyte or acid-base disorders, hypo/hyperglycemia, severeanemia, polycythemia vera, hyperlipidemia, hepatic failure,uremia, pulmonary insufficiency, hypopituarism, thyroid, adrenalor parathyroid dysfunction, cardiac dysfunction, hepatolenticulardegeneration
Intracranial disorders :Cerebrovascular insufficiency, chronic meningitis or encephalitis,neurosyphilis, HIV, epilepsy, tumor, abscess, subdural hematomas, multiple sclerosis, NPH
CAUSES OF TREATABLE DEMENTIA ( lanj’ )
Deficiency states :Vitamin B12 deficiency, folate deficiency, pellagra (niacin)
Collagen-vascular disorders :SLE, temporal arteritis, sarcoidosis, Behcet’s syndrome
Exogenous intoxication :Alcohol, CO, organophosphates, toluene, trichloroethylene, carbon disulfide, lead, mercury, arsenic, thallium, manganese, nitrobenzene, anilines, bromine hydrocarbone
EVALUATION OF THE PATIENT WITH DEMENTIA
Complete history,neurological and general physical
examination
Special emphasis onhistory of drug use
evidence of intoxication,evidence of
systemic disease
Neuropsychologicalexamination
CBC, sedimentation rate,electrolytes, BUN, creatinine,glucose, calcium, phosphate, liver enzymes, vit.B12, folate, thyroid function, serologic testfor HIV and syphilis, urinalysis
ECG, CT-scan, MRI,MRA, MRI-spectroscopy,
SPEC, PET
EEG, AEP, VEPIf available
LP, radioisotopecisternography
if available
Consider cerebral angiographyif CT-scan equivocal of if CVD or
arteritis is suspected
Metastatic work-upif indicated
If indicated –blood gases,
heavy metal andintoxication screen
Gilroy J, 2000
ALZHEIMER DISEASE
- Most common form of dementia
- Caused by progressive neuronal degeneration
- 70% in middle age and elderly individuals
- 1% in age 50-70 years, 50% in very elderly people
- The etiology is unknown
- USA : prevalence is 4 million people over age 65 years
DISEASES OF GRAY MATTER :
ALZHEIMER DISEASE
PATHOLOGICAL APPEARANCE
☺ Amyloid plaquesconsist of β-amyloid peptide (a fragment of precursor protein)
☺ Neurofibrillary tanglesa core of an abnormally phosphorylated form of the microtubule binding protein tau
ALZHEIMER DISEASE
Relationship still intense research
Apo E plasma is synthesized in liver and brain
The role of apo-E is diverse
it regulates lipid metabolism play a part of
atherosclerosis process
The function of apo E in brain is unique
synthesized in astrocytes
The role in dendritic remodeling and
synaptogenesis after brain injury
APOLIPOPROTEIN-E ( Apo E ) with AD
ALZHEIMER DISEASE
Three isoform of apo-E : apo E2, apo E3 and apo E4 ( encoded by a gene located in chromosome 19 ) Apo E gene has three alleles ( apo Ee2 allele, apo Ee3 allele, apo Ee4 allele) Apo Ee4 allele has been associated with HDL or LDL cholesterol and as risk factor of :
Cardiovascular disease Cerebrovascular disease Alzheimer disease Cognitive decline
APOLIPOPROTEIN-E ( Apo E )
Apo Ee3 gene have a protective effect against (sporadic) Alzheimer disease
ALZHEIMER DISEASE
APOLIPOPROTEIN-E ( Apo E )
The current hypothesis of apo Ee4 in AD : As a carrier for Β-amyloid in the formation of amyloid plaque The failure of apo Ee4 to bind to tau protein failure of phosphorylation of tau formation of neurofibrillary tangles ( correlates with severity of AD ) Promoting neuronal loss in the cortex (amyloid deposition, neuronal death and plaque formation)
Apo E gene (in chromosome 19) is associated with asrisk factor and age of onset of AD
DSM-IV DIAGNOSTIC CRITERIA FOR AD
A. The development of multiple cognitive deficits manifested by both : 1). memory impairment 2).One (or more) of the following cognitive disturbances : a). aphasia, b). apraxia, c). agnosia, d). disturbance in executive functioning ( planning, organization, sequencing, abstracting )B. The cognitive deficits in criteria A1 and A2 each cause severe impairment in
social or occupational functioning and represent a major decline from a previous level of functioning
C. The course is characterized by gradual onset and continuing cognitive decline
D. The cognitive deficits in criteria A1 and A2 are not due to any of the following: 1).other central nrvous system conditions that cause progressive deficits in memory and cognition (for example, cerebrovascular disease, Parkinson’s disease, Huntington’s disease, subdural hematoma, NPH, brain tumor), 2).systemic conditions known to cause dementia (for example: hypothyroidism, vit.B12 and folic acid deficiency, niacin deficiency, hypercalcemia, neurosyphilis, HIV infection)
E. The deficits do not occur exclusively during the course of deliriumF. The disturbance is not better accounted for by any other Axis I disorder (for
examp-le: major depressive disorder, schizophenia)
American Psychiatric Association (APA): Diagnostic and Statistic Manual of Mental Disorders 4 th ed, 1994
TREATMENTS
1. Diet2. Adequate care3. Planning with family4. Pharmacotherapy :
Sedation and antidepressant Drug therapy (Tacrine, Donepezil HCl)
PICK DISEASE
Rare type of dementia Characteristic : selective atrophy of frontal and temporal of the brain
( sparing of the superior temporal gyrus ) The atrophy usually symmetrical ( less cases asymmetrical or unilateral atrophy ) Dilatation of frontal and temporal horns of lateral ventricular Neuronal loss in affected areas Surviving neurons are small with argentophilic inclusion ( Pick cells ) Senile plaques and neurofibrillary tangles not a characteristic feature of Pick disease
DISEASES OF GRAY MATTER :
DEMENTIA WITH LEWY BODIES (DLB)
Characteristic : The presence of Lewy bodies
( intracytoplasmic spherical eosinophilic neuronal inclusion
bodies ) in the neuron of brainstem and cerebral cortex The minority of cases with senile plaques and
neurofibrillary tangles
The etiology is unknown
DISEASES OF GRAY MATTER :
DISEASES OF THE BASAL GANGLIA
HUNTINGTON DISEASE ( HUNTINGTON CHOREA )
Hereditary degenerative disease of the CNS Inherited as an autosomal dominant trait Huntington’s allele located in chromosome-4 Brain atrophy, most prominent in frontal lobe Ventricular dilatation (frontal horn of lateral ventricular)
due to atrophy of caudate nucleus All races, prevalence 6.5 cases per 100.000 population The mean age of onset ranges from 35 to 42 years
DISEASES OF GRAY MATTER :
DISEASES OF THE BASAL GANGLIA
HUNTINGTON DISEASE ( lanj’)
Microscopic feature : Loss of medium-sized neurons ( 80%) in caudate
nucleus and putamen Sparing of large neurons Reactive gliosis (predominant astrocytes) Decrease levels of neurotransmitters in striatum :
Subtance-P, GABA, metenkephaline and dynorphin Pathomechanism :
Imbalance productive and removal of free radical cause by gene mutation neuronal death Gene defect failure of energy metabolism at the mitochondrial level neuronal death
DISEASES OF THE BASAL GANGLIA
HUNTINGTON DISEASE ( lanj’)
Clinical features : Emotional disorders of depression Irritability Apathy Cognitive disturbance (slowly progressive dementia) Motor symptoms (choreathetosis, rigidity and bradykinesia)
Two variants 1. Westphal. Rapid form of Huntington disease: motor symptoms and dementia death in few years after onset2. Juvenile. Occurs in children and adolescent death in few years after onset
PROGRESSIVE SUPRANUCLEAR PALSY
DISEASES OF THE BASAL GANGLIA
Chronic progressive brain disease Etiology unknown, maybe related to exogenous toxin Decreased pigment in substansia nigra, locus
ceruleus, neuronal loss in basal ganglia, brainstem and cerbellum
Neurofibrillary tangle in the brain Prevalence 1.4 cases per 100.000 Inherited as suggesting an autosomal dominant
trait Survival following onset is from 6 to 9 years
PROGRESSIVE SUPRANUCLEAR PALSY
DISEASES OF THE BASAL GANGLIA
Clinical features : Supranuclear ophthalmoplegia (chiefly vertical gaze) Pseudobulbar palsy Neck dystonia (prominent) , axial dystonia Behavioral and cognitive disturbance Parkinsonism Gait disturbance Dysequilibrium and falls
PROGRESSIVE SUPRANUCLEAR PALSY
DISEASES OF THE BASAL GANGLIA
TREATMENT :
Levodopa (in the early stage, relative high dose – up to
1500 mg 24hr without adverse effects
Amitriptyline (beginning 10 mg and increased up to 100
mg)
Amantadine
DISEASES OF GRAY MATTER :
MOTOR NEURON DISEASE(Amyotrophic Lateral Sclerosis)
Chronic disease with progressive degeneration of motor neuron in :
Anterior horn of spinal cord Motor nuclei in brainstem Motor area in posterior aspect of frontal lobe
( precentralis gyrus ) Etiology unknown, may be result of exotoxicity Inherited as autosomal dominant or autosomal
recessive trait (with gene located in chromosome-21, some cases in chromosome-2)
Prevalence 2 per 100.000, M-F ratio = 1.1:1 The median onset is 66 years
DISESES OF GREY MATTER
DISEASES OF BASAL GANGLIA
- Progressive Supranuclear Palsy
- Multiple System Atrophy
- Olivopontocerebellar Atrophy