This document discusses degenerative diseases and focuses on motor neuron disease (MND). It defines MND as the progressive degeneration of motor neurons in the spinal cord, brain stem, and motor cortex. The document covers the pathology, epidemiology, genetics, clinical features, investigations, management, and prognosis of MND. It describes different variants of MND including amyotrophic lateral sclerosis, primary lateral sclerosis, progressive muscular atrophy, and bulbar onset disease. No cure currently exists for MND, though riluzole has been shown to modestly prolong survival.

1. DEGENERATIVE DISEASES
DR M SHOAIB SHAFI

2. DEGENERATIVE DISEASES
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Alzheimers disease
Motor neuron disease
Wernickes- korsakoff disease
Parkinsonism
Multiple system atrophy
Progressive supranuclear palsy
Wilsons disease
Huntingtons disease
Hereditary ataxias
spinal muscular atrophies

3. ALZHEIMERS DISEASE
• Most common cause of dementia, occuring
mostly in patients over 45 years.
• 15% cases are familial divided into 2 groups ie
1)Early onset: autosomal dominant
2)Later-onset: inheritance not so clear
• Genetic abnormalities on several different
chromosomes have been identified.

4. PATHOLOGY
• MACROSCOPICALLY; brain is atrophic
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particularly cerebral cortex & hippocampus.
MICROSCOPY reveals senile plaques and
neurofibrillary tangles in cerebral cortex.
There is significant quantity of AMYLOID in the
plaques.
There are different neurotransmitter
abnormalities especially in cholinergic
transmission.

5. CLINICAL FEATURES
• The key clinical feature is impairment of delayed
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recall ie inability to retrieve information acquired
in the past.
Both short term & long term memory are
affected especially short term.
Later apraxia, visuospatial impairment and
aphasia develop.
Anosogonosia
depression

6. Investigations
• No diagnostic lab test
• Investigations can be done to rule out other
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causes
Baseline labs
CT / MRI brain
TFTs
Vitamin B12 levels
EEG
ANA / anti- ds DNA

7. TREATMENT
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Conservative treatment
Psychosocial support
Antidepressants
Anticholinestrases:
Donepezil
Rivastigmine
Galantamine
NMDA receptor antagonist MEMANTINE

10. DEFINITION
• This is a progressive disorder of unknown cause
in which there is degeneration of motor neurons
in the spinal cord & cranial nerve nuclei, and of
pyramidal neurons in the motor cortex.
• French neurologist Jean Martin Charcot first
described the term of MND in 1869. so also
called as Maladie de charcot in France.

11. Description
• Affects the nerves responsible
for movement.
The nerve cells
gradually degenerate
and cause the
muscles to weaken
and waste away.

12. PATHOLOLOGY
• > 90% of the cases are sporadic.
• 5 to 10 % are familial showing autosomal
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dominant inheritance.
The genetic defect lies on chromosome 21 and
the enzyme involved is superoxide dismutase
(SOD1) in about 20% of familial cases.

13. EPIDEMIOLOGY
• The incidence of MND is approximately 1–5 out
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of 100,000 people.
Men have a slightly higher incidence rate than
women.
Mostly presents in 4th or 5th decade.
Cases under the age of 50 years are called
"young onset MND“.
Tentative environmental risk factors identified so
far include: exposure to severe electrical shock
leading to coma, having served in the first
Gulf War, and playing professional
football (soccer).

14. HOT-SPOTS OF MND
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There are three "hot spots" of MND in the world.
One is in the Kii peninsula of Japan,
one amongst a tribal population in
Papua New Guinea.
Chamorro inhabitants from the island of Guam in
the Pacific Ocean have an increased risk of
developing a form of MND known as Guamanian
ALS-PD-dementia complex or "lytico bodig“.
Putative theories involve neurotoxins in the
traditional diet including cycad nut flour and bats
that have eaten cycad nuts.

15. PATHOPHYSIOLOGY
• . On macroscopic pathology, there is a degeneration of
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the ventral horns of the spinal cord, as well as atrophy of
the ventral roots. In the brain, atrophy may be present in
the frontal and temporal lobes.
On microscopic examination, neurones may show
spongiosis, the presence of astrocytes, and a number of
inclusions including characteristic "skein-like" inclusions,
bunina bodies, and vacuolisation.
There is a role in excitotoxicity and oxidative stress,
presumably secondary to mitochondrial dysfunction. In
animal models, death by apoptosis has also been
identified.

17. CLINICAL FEATURES
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Usually there is a combination of upper & lower
motor neuron features without sensory
involvement.
The presence of brisk reflexes in wasted
fasciculating muscles is typical.

18. SYMPTOMS
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Limb muscle weakness
Cramps
Ataxia
Difficulty in holding the objects
Difficulty in speaking
Difficulty in eating

19. SIGNS
• Wasting & fasciculation of muscles
• Weakness of muscles of limb, tongue, face and
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palate
Spasticity, exaggerated reflexes and extensor
plantar response (pyramidal tract involvement)
No sensory deficitextraocular muscles &
sphincters remain intact till very late stages.
No intellectual impairment or depression in most
of the cases.

20. COURSE
Symptoms usually begin focally in one
part and spread gradually but relentlessly
to become widespread.

21. VARIANTS OF MND
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Forms of motor neuron disease include:
amyotrophic lateral sclerosis (ALS) (sometimes
called Lou Gehrig's disease)
• primary lateral sclerosis (PLS)
• progressive muscular atrophy (PMA)
• Bulbar:
– pseudobulbar palsy - spastic
– progressive bulbar palsy - spastic and flaccid

22. • MND in the presence of both upper and lower
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motor neuron degeneration is ALS.
Where the illness affects only the upper motor
neurons it is PLS.
Where the illness affects only the lower motor
neurons it is PMA.
Progressive bulbar palsy is degeneration of the
lower motor neurons innervating the bulbar
region (mouth, face, and throat).
Pseudobulbar palsy refers to degeneration of the
upper motor neurons to the same region.

23. PROGRESSIVE MUSCULAR
ATROPHY
• Predominantly spinal motor neurons affected
• Weakness and wasting of distal limb muscles at
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first
Fasciculation in muscles
Tendon reflexes may be absent

24. PRIMARY LATERAL SCLEROSIS
• This form presents with weaknessof limbs.
O/E there are all the features of UMN
lesion ie spasticity, brisk reflexes and
upgoing plantars.
• It is purely an UMN variant.

25. AMYOTROPHIC LATERAL
SCLEROSIS
• Frequently called Lou Gehrig’s disease.
In memory of
the famous
baseball player
Lou Gehrig, who
died from ALS in
1941.
Lou Gehrig
Photo from Gehrig’s
homepage

26. AMYOTROPHIC LATERAL
SCLEROSIS
• Amyotrophic comes from the Greek language: A- means
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"no", myo refers to "muscle",
trophic means "nourishment";
amyotrophic means "no muscle nourishment," which
describes the characteristic atrophication of the sufferer's
disused muscle tissue.
Lateral identifies the areas in a person's spinal cord
where portions of the nerve cells that are affected are
located. As this area degenerates it leads to scarring or
hardening ("sclerosis") in the region.

27. BULBAR LESIONS
• There is involvement of tongue, palate and
pharyngeal muscles leading to dysarthria
and dysphagia.
• There may be bulbar palsy (LMN lesion)
• Or pseudobulbar palsy ie UMN lesion.

28. DIFFERENCES BETWEEN BULBAR &
PSEUDOBULBAR PALSY
• BULBAR PALSY
• Tongue is flaccid &
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fasciculating
Jaw jerk is normal or
absent
Speech is nasal or
hoarse
• PSEUDOBULBAR
• Tongue is spastic
• Jaw jerk is increased
• Speech is like Donald
Duck

29. DIAGNOSIS
• Diagnosis is clinical.
• Investigations are done only to rule out
other diseases.

30. INVESTIGATIONS
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CT / MRI brain
EMG
NCS
SPINAL IMAGING

31. MANAGEMENT
•NON-PHARMACOLOGICAL MEASURES
• PHARMACOLOGICAL MEASURES

32. GENERAL MEASURES
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Physiotherapy
Psychotherapy
Speech therapy & communication devices
Occupational assisstance
Splints, walking aids
Wheelchairs
Percutaneous gastrostomy
Non-invasive ventilatory support

34. DRUGS
• Riluzole ;a glutamine receptor antagonist;
100 mg/ day is modestly effective in
prolonging life by upto 2 months.
• Nerve growth factor
• Insulin like growth factor 1 (IGF-1)

35. RESEARCH WORK
• The search for a drug that will slow MND
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progression is under way. For example, recent
research using mouse models suggests that
minocycline, a common antibiotic, may also be
effective in extending the lifespan of MND
sufferers.
Minocycline extends the lifespan of MND mice
with SOD1 mutations, but it does not prevent
their eventual death. Other agents that are
currently in trials include ceftriaxone,
arimoclomol and coenzyme Q10.

36. PROGNOSIS
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It is a progressive disease.
Mean time from diagnosis to death is 1 year.
Most patients die within 3 to 5 years of onset of
illness.
Younger patients & those with bulbar symptoms
show a more rapid course.
Death is usually from respiratory infections &
complications of immobility.

37. FAMOUS PERSONS WITH MND
• JASON BECKER
• PROF STEPHEN HAWKING