Degenerative diseases

1. DEGENERATIVE DISEASESDEGENERATIVE DISEASES
DR M SHOAIB SHAFIDR M SHOAIB SHAFI

2. DEGENERATIVE DISEASESDEGENERATIVE DISEASES
•Alzheimers diseaseAlzheimers disease
•Motor neuron diseaseMotor neuron disease
•Wernickes- korsakoff diseaseWernickes- korsakoff disease
•ParkinsonismParkinsonism
•Multiple system atrophyMultiple system atrophy
•Progressive supranuclear palsyProgressive supranuclear palsy
•Wilsons diseaseWilsons disease
•Huntingtons diseaseHuntingtons disease
•Hereditary ataxiasHereditary ataxias
•spinal muscular atrophiesspinal muscular atrophies

3. ALZHEIMERS DISEASEALZHEIMERS DISEASE
•Most common cause of dementia, occuring Most common cause of dementia, occuring
mostly in patients over 45 years.mostly in patients over 45 years.
•15% cases are familial divided into 2 groups ie15% cases are familial divided into 2 groups ie
1)Early onset: autosomal dominant1)Early onset: autosomal dominant
2)Later-onset: inheritance not so clear2)Later-onset: inheritance not so clear
•Genetic abnormalities on several different Genetic abnormalities on several different
chromosomes have been identified.chromosomes have been identified.

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

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

6. InvestigationsInvestigations
•No diagnostic lab testNo diagnostic lab test
•Investigations can be done to rule out other Investigations can be done to rule out other
causescauses
•Baseline labsBaseline labs
•CT / MRI brainCT / MRI brain
•TFTsTFTs
•Vitamin B12 levelsVitamin B12 levels
•EEGEEG
•ANA / anti- ds DNAANA / anti- ds DNA

7. TREATMENTTREATMENT
•Conservative treatmentConservative treatment
•Psychosocial supportPsychosocial support
•AntidepressantsAntidepressants
•Anticholinestrases:Anticholinestrases:
DonepezilDonepezil
RivastigmineRivastigmine
GalantamineGalantamine
•NMDA receptor antagonist NMDA receptor antagonist MEMANTINEMEMANTINE

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

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

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

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

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

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

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

18. SYMPTOMSSYMPTOMS
•Limb muscle weaknessLimb muscle weakness
•CrampsCramps
•AtaxiaAtaxia
•Difficulty in holding the objectsDifficulty in holding the objects
•Difficulty in speakingDifficulty in speaking
•Difficulty in eatingDifficulty in eating

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

20. COURSECOURSE

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

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

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

23. PROGRESSIVE MUSCULAR PROGRESSIVE MUSCULAR
ATROPHYATROPHY
•Predominantly spinal motor neurons affectedPredominantly spinal motor neurons affected
•Weakness and wasting of distal limb muscles at Weakness and wasting of distal limb muscles at
firstfirst
•Fasciculation in musclesFasciculation in muscles
•Tendon reflexes may be absentTendon reflexes may be absent

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

25. AMYOTROPHIC LATERAL AMYOTROPHIC LATERAL
SCLEROSISSCLEROSIS
•Frequently Frequently called Lou Gehrig’s disease.
In memory of In memory of
the famous the famous
baseball player baseball player
Lou Gehrig, who Lou Gehrig, who
died from ALS in died from ALS in
1941.1941.
Lou Gehrig
Photo from Gehrig’s
homepage

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

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

28. DIFFERENCES BETWEEN BULBAR & DIFFERENCES BETWEEN BULBAR &
PSEUDOBULBAR PALSYPSEUDOBULBAR PALSY
•BULBAR PALSYBULBAR PALSY
•Tongue is flaccid & Tongue is flaccid &
fasciculatingfasciculating
•Jaw jerk is normal or Jaw jerk is normal or
absent absent
•Speech is nasal or Speech is nasal or
hoarsehoarse
•PSEUDOBULBARPSEUDOBULBAR
•Tongue is spasticTongue is spastic
•Jaw jerk is increasedJaw jerk is increased
•Speech is like Donald Speech is like Donald
DuckDuck

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

30. INVESTIGATIONSINVESTIGATIONS
•CT / MRI brainCT / MRI brain
•EMGEMG
•NCSNCS
•SPINAL IMAGINGSPINAL IMAGING

31. MANAGEMENTMANAGEMENT
•PHARMACOLOGICAL MEASURESPHARMACOLOGICAL MEASURES
•NON-PHARMACOLOGICAL MEASURES

32. GENERAL MEASURESGENERAL MEASURES
•PhysiotherapyPhysiotherapy
•PsychotherapyPsychotherapy
•Speech therapy & communication devicesSpeech therapy & communication devices
•Occupational assisstanceOccupational assisstance
•Splints, walking aidsSplints, walking aids
•WheelchairsWheelchairs
•Percutaneous gastrostomyPercutaneous gastrostomy
•Non-invasive ventilatory supportNon-invasive ventilatory support

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

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

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

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