DJADJANG SUHANA BAGIAN ILMU PENYAKIT SARAF FKUP - RSHS

DEGENERATIVE DISEASES
Penyakit degeneratif SSP dapat mengenai : 1. Substansia abu 2. Substansia putih 3. 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

I. DISEASES OF GREY MATTER

DISEASES OF THE CEREBRAL CORTEX :

DEMENTIA

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 Dementia

1. 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, severe anemia, polycythemia vera, hyperlipidemia, hepatic failure, uremia, pulmonary insufficiency, hypopituarism, thyroid, adrenal or parathyroid dysfunction, cardiac dysfunction, hepatolenticular degeneration 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, Behcets 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 Neuropsychological examination Special emphasis on history of drug use evidence of intoxication, evidence of systemic disease

CBC, sedimentation rate, electrolytes, BUN, creatinine, glucose, calcium, phosphate, liver enzymes, vit.B12, folate, thyroid function, serologic test for HIV and syphilis, urinalysis

ECG, CT-scan, MRI, MRA, MRI-spectroscopy, SPEC, PET

EEG, AEP, VEP If available

If indicated blood gases, heavy metal and intoxication screen

LP, radioisotope cisternography if available

Metastatic work-up if indicated

Consider cerebral angiography if CT-scan equivocal of if CVD or arteritis is suspected

Gilroy J, 2000

DISEASES OF GRAY MATTER :

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

ALZHEIMER DISEASE
PATHOLOGICAL APPEARANCE

Amyloid plaques consist of -amyloid peptide (a fragment of precursor protein) Neurofibrillary tangles a core of an abnormally phosphorylated form of the microtubule binding protein tau

ALZHEIMER DISEASE
APOLIPOPROTEIN-E ( Apo E ) with AD 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

ALZHEIMER DISEASE
APOLIPOPROTEIN-E ( Apo E ) 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
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 -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 as risk 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, Parkinsons disease, Huntingtons 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 delirium F. 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. Diet 2. Adequate care 3. Planning with family 4. Pharmacotherapy : Sedation and antidepressant Drug therapy (Tacrine, Donepezil HCl)

DISEASES OF GRAY MATTER :

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

Huntingtons 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 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 onset 2. Juvenile. Occurs in children and adolescent death in few years after onset

DISEASES OF THE BASAL GANGLIA PROGRESSIVE SUPRANUCLEAR PALSY 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

DISEASES OF THE BASAL GANGLIA PROGRESSIVE SUPRANUCLEAR PALSY

Clinical features :
Supranuclear ophthalmoplegia (chiefly vertical gaze) Pseudobulbar palsy Neck dystonia (prominent) , axial dystonia Behavioral and cognitive disturbance Parkinsonism Gait disturbance Dysequilibrium and falls

DISEASES OF THE BASAL GANGLIA PROGRESSIVE SUPRANUCLEAR PALSY 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

DISEASES OF GRAY MATTER :

MOTOR NEURON DISEASE

(Amyotrophic Lateral Sclerosis)

DISESES OF GREY MATTER

DISEASES OF BASAL GANGLIA - Progressive Supranuclear Palsy
- Multiple System Atrophy - Olivopontocerebellar Atrophy