Degenerative and Non-infectious

diseases of the Central Nervous

System-Laboratory diagnosis.
Prof. Victor Mwanakasale
(BSc, MB,ChB, MSc, Dip, PhD)
MBS 340 (2023- 2024)
Objective of the lecture.
• To learn the laboratory investigations in
the diagnosis of Degenerative and Non-
infectious diseases of the Central Nervous
System.
Format of the lecture.
1. Degenerative diseases of the CNS in
general.
2. Dementia
3. Examples of degenerative and non-
infectious diseases and their specific
laboratory Investigations.
Degenerative diseases of the CNS.
• Degeneration*:
is a deterioration in form.
Types of degeneration*:
1. True degeneration.
2. Infiltration.
• Degeneration also called retrogression.
Pathology in degenerative diseases*.
• Loss of neurons and secondary gliosis.
• Often affect people in the prime of life.
• From extremely common e.g. Alzheimer
disease to rare e.g. spinocerebellar
ataxia.
Dementia*.
• Defn
• Age: > 65 years
• Not normal stage in aging
• Causes: (Other than process of aging)
• Symptoms:
Examples of DD of CNS
1. Alzheimer disease
2. Picks disease
3. Amyotrophic lateral sclerosis
4. Muscular dystrophies (Duchenne , Limb
girdle, Facioscapulohumeral, Mytonic)
5. Prion diseases
I. vCreutzfeldt-Jakob disease (Scrapie,
Kuru, Bovine spongiform encephalopathy
(Mad cow disease))
II. cCreutzfeldt-Jakob disease.
6. Spinocerebellar ataxia.
7. Parkinson’s disease
8. Multiple sclerosis
Alzheimer disease*.
• A presenile dementing illness.
• At risk:
I. Age
II. Familial tendency in some families
-Beta amyloid gene mutation.
• Characterised by loss of recent memory.
Laboratory diagnosis of AD*.
• No definitive laboratory diagnostic test
for Alzheimer disease.
• Pathologic diagnosis (Histopathology)
only definitive method.
1. Cerebral Spinal Fluid examination :
a) Tau proteins (↓)
b) Beta amyloid (↑)
2. Laboratory tests to rule out any other
cause of dementia such as:
i. Thyroid Function tests
ii. Vitamin B-12 levels
iii. Folate levels
iv. Tests for syphilis
v. HIV
vi. Creutzfeldt-Jakob disease (CJD)
3. Other non-specific Investigations:
a) Full blood count
b) Plasma Electrolytes
c) Electrocardiogram (ECG)
d) Electroencephalogram (EEG).

4. Imaging:
e) CT scan
f) MRI
g) Chest X-ray
Prion diseases*
• Creutzfeldt-Jakob Disease (CJD).
Two types:
1. Classical (cCJD)
2. Variant (vCJD)
vCJD*.
Mad cow disease (BSE).
• Transmissible, slowly progressive,
degenerative, fatal (CNS) disease of adult
cattle.
Causative agent: Prion, is an infectious
protein.
In humans.
• Agent for BSE in cattle causes vCJD in
people.
cCJD*.
• 3 types:
1) Sporadic
2) Familial
3) Iatrogenic
Characteristic differences between cCJD
and vCJD*.
1. Median age at death
2. Median duration of illness
3. Clinical signs and symptoms
4. EEG changes
Diagnosis.
1. Laboratory diagnosis:*.
a) Serology not useful.
b) CSF examination for 14-3-3 proteins* (Raised in
cCJD).
c) Prion detection by Protein Misfolding Cyclic
Amplification (PMCA) in plasma-latest*.

2. EEG.-Central in the diagnosis of CJD

3. Histology: Autopsy brain tissue/biopsy.

4. Imaging: Skull X-ray, CT scan, or MRI (late brain

abnormalities)*.
Muscular dystrophies*
• Non-inflammatory degeneration of
muscles.
• Duchenne muscular dystrophy the
commonest type.(sex-linked recessive).
• Pseudo hypertrophy and weakness
progress from early childhood.
Laboratory diagnosis*.
i. Blood tests for enzymes:
a) Creatine phosphokinase (CPK) (↑)
b) Aldolase (↑).
ii. Genetic testing on blood samples- can
confirm the diagnosis*.
Other investigations.
i. Muscle biopsy.
ii. Electrocardiogram (ECG or EKG)
Amyotrophic lateral sclerosis (ALS)*
Also known as motor neurone disease.
• A debilitating disease.
• Characteristics:*
Diagnosis*
1. Clinical diagnosis (symptoms and
signs)-basis for diagnosis.
2. Laboratory diagnosis:
a) Blood tests-Enzymes (CPK, Ald)
b) CSF examination (↑total proteins)
3. Electromyogram (EMG)
4. Radiological imaging: MRI, X-Ray of
vertebral column
Spinocerebellar ataxia.
• Hereditary and progressive.
• Ataxia is a dominant symptom.
• Spinocerebellar ataxia type 1 (SCA1)
• Is autosomal dominant
Laboratory diagnosis.
1. Genetic Testing.
• ATXN1 - the only gene in which
mutations are known to cause SCA1.
• Detects 100% of all cases.
Parkinson’s disease (Parkinsonism)*.
• “Shaking palsy”
• Also known as “paralysis agitans”
• Clinical syndrome:
Diagnosis*.
i. Clinical diagnosis
ii. Laboratory diagnosis:
• Blood examination: NAD
ii. EEG .
iii. MRI, CT scan-remarkable and exquisite
anatomical pictures.
FIN