Neurodegenerative disorders

Dr. Mehzabin Ahmed

These are diseases of the nervous system that
are characterized by a progressive loss of
neurons and an associated secondary change
in the white matter.

The diseases arise without any inciting event.

The neuronal loss is selective and affects one

or more groups of neurons.

The clinical manifestations thus depend on the

group of neurons involved.
 Degenerative diseases affecting
the cerebral cortex
Eg, Alzheimers disease, Picks disease.
The predominant manifestations are those of
dementia.

Dementia is a neurological illness in which the

patient suffers progressive loss of memory,
judgment, and awareness.

It may be accompanied by problems with

speech, social behaviors, toileting, and walking.
 The patient is frequently unaware of changes that
the family members notice as declines in daily
living skills and memory, or alterations in
personality and reasoning ability.

Since there are many different kinds of dementia,

accurate diagnosis is important.

Some forms of dementia are treatable, while

others are not.

Alzheimer's Disease is the most common cause of

dementia in the elderly.
Manifestations depend on the lobes involved
and the corresponding loss of normal functions
carried out by the neurons in the lobe.

For example:
 involvement of the frontal lobe results in the
loss of cognitive functions, mathematical
skills, memory, etc,
 involvement of the temporal lobe results in
language deficits and speech and hearing,
 occipital lobe involvement results in visual
disturbances.
 Alzheimers disease
Part of brain involved- Cerebral cortex

Pathogenesis-
Deposition of β amyloid chains in the brain
parenchyma
Genes on chromosome 21 play an important role

Characteristic morphology-
Cerebral atrophy with presence of neuritic
plaques and neurofibrillary tangles
Salient clinical Loss of interest
findings- Slow
progression. Starts Inability to think clearly
as forgetfulness Substandard performance
and memory Wide variation in mood
disturbances,
language deficits, Loss of recent memory
loss of Disorientation
mathematical & Lack of insight
learned motor
skills. Finally the Loss of all intellects
patient becomes Slurred speech, aphasia
incontinent and Vegetative
mute and is unable
to walk. Death by pneumonia, etc.
Alzheimer’s disease:
1) Generalized atrophy of cerebral cortex
2) Widening of the cerebral sulci is most pronounced in the frontal,
temporal and parietal lobes and dilatation of the ventricles
 Granulovacuolar
degeneration appears as tiny
vesicles with central, dense
cores. It is typical of
Alzheimer's disease

Neurofibrillary tangles- The cytoskeletal

filaments are grouped together in the
elongated pink tangles
 Picks disease- Lobar atrophy
Part of brain involved- Frontal and temporal
lobes
Pathogenesis- Some cases are familial & linked
to genetic abnormality
Characteristic morphology- Atrophy of the
cerebrum giving it a Knife like appearance
Presence of Pick body in the neuron
Salient clinical findings- Starts as behavioral
disturbances & alteration of personality &
language disturbances
Asymmetric atrophy of frontal and temporal lobes with sparing of
temporal lobes- Knife edge gyri

Pick cells
with Pick
bodies

Balloon neurons,
swollen for unknown
reason, are typical of
Pick's
Degenerative diseases affecting
the basal ganglia & brainstem
Eg, Parkinson disease, Huntingtons disease.

The predominant manifestations are those

of gait disturbances.
 Parkinson disease
Part of brain involved- Substantia nigra
Pathogenesis- Loss of dopaminergic neurons,
either due to a genetic abnormality or secondary
to
 Drugs (reserpine, phenothiazine, MPTP)
 Post-encephalitic (encephalitis lethargica)
 Atherosclerotic
 Manganese intoxication
 CO poisoning
 “Punch-drunk syndrome”- Professional boxers
Characteristic morphology- Loss of
pigmentation and atrophy of the midbrain
Lewy bodies in the neurons
Salient clinical findings: Presents with
 dementia,

 cog wheel rigidity,

 shuffling gait and

 mask like face

 Akinesia/Bradykinesia

 Tremor (resting)

 Pill-rolling

 Stooped posture

 Festinating gait
•Loss of pigments and neurons of substantia nigra (s.n.) and locus
ceruleus (l.c.)
•Lewy bodies- laminated intracytoplasmic inclusion bodies
composed of α-synuclein in neurons of s.n. and l.c.
•Decrease in Dopamine in s.n. and neostriatum
 Huntington disease
Part of brain involved- Cerebral cortex
Pathogenesis- Genetic disease with an autosomal
dominant inheritance which produces an
abnormal protein Huntingtin
Characteristic morphology- Atrophy of the
caudate and ventricular dilation Loss of neurons
from caudate & putamen
Salient clinical findings- Causes movement
disorder (chorea- uncontrolled rapid jerky
movements), dementia and behavioral
disturbances
Cerebral atrophy in the region of the caudate and putamen
and ventricular dilatation
 Degenerative diseases affecting
the Spinocerebellar tracts
Eg, Freidrichs ataxia, ataxia telangiectasia.

These diseases result in the loss of balance

and coordinated movements (ataxia),
abnormal tonicity and posture
abnormality
 Freidrich ataxia
Part of brain involved- Brainstem, spinal cord
and cerebellum

Pathogenesis- An autosomal recessive disorder

Characteristic morphology- Degeneration of

neurons and loss of axons in the spinal cord
and the spinocerebellar tracts
Salient clinical findings-
 Begins in the 1st decade as gait ataxia,
clumsy hands, dysarthria, decreased deep
tendon reflexes and positive Babinski test.
 There is also a loss of joint position,
vibratory sense, and pain & temperature
sensation.
 They get wheel chair bound in 5yrs time
from the onset of the symptoms.
 They may have CCF and arrhythmias
 Degenerative diseases affecting
the motor neurons
Eg, Amyotropic lateral sclerosis. The
involvement of the neurons can be of the
upper motor (Betz cells in the motor cortex
in the cerebrum) or the lower motor type
(neurons in the nuclei of the cranial nerves
or the neurons of the motor nerves).

It results in progressive weakness and

atrophy of the muscles supplied by the
affected nerves
 Amyotropic lateral sclerosis
Part of brain involved- Anterior horn cells in
the spinal cord, Betz cells and cranial motor
nuclei
Pathogenesis- Unknown etiology with
sporadic incidence in most cases and in a few
an autosomal dominant pattern of inheritance
is seen
Characteristic morphology- Loss of upper
motor neurons, there is lateral column
degeneration with gliosis, the so-called
"sclerosis" of the lateral columns of spinal cord
Salient clinical findings-
 Weakness and paralysis of the
extremities and may go on to develop
bulbar signs and symptoms.
 The course is usually 2 to 6 years after
diagnosis, but patients presenting with
bulbar signs and symptoms (difficulty
in swallowing and phonation) have a
shorter life span because of swallowing
difficulties and aspiration.
Negri bodies in the Spongiform change consists of watery vacuoles
cytoplasm in rabies in the perikaryons and processes of neurons. It's
typical of the prion diseases.
 Overview
Cerebral cortex Alzheimer disease
Picks disease

Basal ganglia & Parkinson disease

cerebellum Huntington disease

Spinocerebellar Fredreichs ataxia

tracts Ataxia telengiectasia

Motor neurons Amyotropic lateral

sclerosis