Degenerative Disorders Of The Cns

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 PathogenesisDeposition of β amyloid chains in the brain parenchyma Genes on chromosome 21 play an important role Characteristic morphologyCerebral atrophy with presence of neuritic plaques and neurofibrillary tangles

Salient clinical findings- Slow progression. Starts as forgetfulness and memory disturbances, language deficits, loss of mathematical & learned motor skills. Finally the patient becomes incontinent and mute and is unable to walk.

Loss of interest Inability to think clearly Substandard performance Wide variation in mood Loss of recent memory Disorientation Lack of insight Loss of all intellects Slurred speech, aphasia Vegetative 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 cytoplasm in rabies

Spongiform change consists of watery vacuoles in the perikaryons and processes of neurons. It's typical of the prion diseases.

Overview Cerebral cortex

Alzheimer disease Picks disease

Basal ganglia & cerebellum

Parkinson disease Huntington disease

Spinocerebellar tracts

Fredreichs ataxia Ataxia telengiectasia

Motor neurons

Amyotropic lateral sclerosis