Saba Parvin Haque

MSc in Neuroscience
from “Sophia College For
https://www.youtube.com/chann
Women”, Mumbai. el/UCAiarMZDNhe1A3Rnpr_WkzA
 Parkinson’s Disease (PD)
Spinal Muscular Atrophy (SMA)

Duchenne Muscular Dystrophy (DMD)

Huntington’s Disease (HD)
Multiple Sclerosis (MS)
Amyotrophic Lateral Sclerosis (ALS)
Neuropathy
❑Parkinson disease is a progressive disorder of the
nervous system. Dr. James Parkinson (1817)
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❑It is second most common Neurodegenerative

disease after Alzheimer’s disease.
❑The disorder affects several regions of the brain,
especially an area called the substantia nigra
(dopamine) that controls balance and movement.
❑Late-onset disease- after age 50
❑Early-onset disease- before age 50
❑Juvenile-onset disease- before age 20
❑Parkinson disease affects more than 1 million people
in North America and more than 4 million people
worldwide.

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 Symptoms https://images.app.goo.gl/KN2gAr6F7N1aaPHm8

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There are currently no blood or laboratory tests to diagnose nongenetic cases of

Parkinson's disease. Diagnosis is based on a person's medical history and a
neurological examination.
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▪ Most cases of Parkinson disease probably result from a complex interaction of

environmental and genetic factors.
▪ Approximately 15 percent of people with Parkinson disease have a family
history of this disorder. Familial cases of Parkinson disease can be caused by Figure: Release of the
mutations in the LRRK2 (leucine rich repeat kinase 2), PARK7 neurotransmitter
(Parkinsonism associated deglycase), PINK1 (PTEN induced kinase 1), dopamine from a neuron
PRKN (parkin RBR E3 ubiquitin protein ligase), or SNCA (synuclein https://medlineplus.gov/images/PX0000KC
_PRESENTATION.jpeg
alpha) gene, or by alterations in genes that have not been identified. Mutations
in some of these genes may also play a role in cases that appear to be sporadic
(not inherited).
▪ Many Parkinson disease symptoms occur when nerve cells (neurons) in the
substantia nigra die or become impaired. Normally, these cells produce a
chemical messenger called dopamine, which transmits signals within the brain
to produce smooth physical movements. When these dopamine-producing
neurons are damaged or die, communication between the brain and muscles Figure: Microscopic
weakens. Eventually, the brain becomes unable to control muscle movement. view of a Lewy body
https://medlineplus.gov/images/
▪ The protein deposits called Lewy bodies appear in dead or dying dopamine- PX0000I4_PRESENTATION.jpeg
producing neurons. (When Lewy bodies are not present, the condition is
sometimes referred to as parkinsonism.) It is unclear whether Lewy bodies play
a role in killing nerve cells or if they are part of the cells' response to the disease.
 https://images.app.goo.gl/xPBgu1wibGVBuqh99

❑ Among familial cases of Parkinson disease, the

inheritance pattern differs depending on the gene that is
altered. If the LRRK2 or SNCA gene is involved, the
disorder is inherited in an autosomal dominant
pattern, which means one copy of an altered gene
in each cell is sufficient to cause the disorder. In most
cases, an affected person has one parent with the
condition.

❑ If the PARK7, PINK1, or PRKN gene is involved,

Parkinson disease is inherited in an autosomal
recessive pattern. This type of inheritance means
that two copies of the gene in each cell are altered.
Most often, the parents of an individual with autosomal Figure: Autosomal dominant Figure: Autosomal recessive
recessive Parkinson disease each carry one copy of the inheritance inheritance
https://medlineplus.gov/images/PX000 https://medlineplus.gov/images/P
altered gene but do not show signs and symptoms of the 09C_PRESENTATION.jpeg X0000A4_PRESENTATION.jpeg
disorder.
 TREATMENT

Medicines prescribed for Parkinson's include:

•Drugs that increase the level of dopamine in the brain
•Drugs that affect other brain chemicals in the body
•Drugs that help control nonmotor symptoms

Deep Brain Stimulation

(DBS)
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❑ It is a genetic neuromuscular disorders.

❑ It is caused by a loss of specialized nerve cells, called motor
neurons that control muscle movement.
❑ The loss of motor neurons causes progressive muscle
weakness and loss of movement due to muscle wasting
(atrophy).
❑ The weakness tends to be more severe in the muscles that are
close to the center of the body (proximal) compared to
muscles away from the body's center (distal).
❑ Breathing and swallowing may also become difficult as the
disease progresses in many types of SMA.
❑ The muscle weakness usually worsens with age.
❑ Spinal muscular atrophy affects 1 per 8,000 to 10,000 people
worldwide.
 There are many types of spinal muscular atrophy that are
caused by changes in the same genes.

❑ Spinal muscular atrophy type 0 {before birth} Rare

❑ Spinal muscular atrophy type I/ (Werdnig-Hoffmann
disease) {at birth or within the first few months of life} Most
common
❑ Spinal muscular atrophy type II/ (Dubowitz disease)
{children between ages 6 and 12 months} Common
❑ Spinal muscular atrophy type III/ (Kugelberg-Welander
disease) {after early childhood} Common
❑ Spinal muscular atrophy type IV {early adulthood} Rare

Diagnosis of SMA is suspected by symptoms and https://medlineplus.gov/images/PX0000T0_PRESENTATION.jpeg

confirmed by genetic testing.

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❑ Mutations in the SMN1 gene cause all types of spinal muscular atrophy.
❑ The number of copies of the SMN2 gene modifies the severity of the
condition and helps determine which type develops.
❑ The SMN1 and SMN2 genes both provide instructions for making a protein
called the survival motor neuron (SMN) protein.
❑ The SMN protein is one of a group of proteins called the SMN complex,
which is important for the maintenance of motor neurons.
❑ Motor neurons transmit signals from the brain and spinal cord that tell
skeletal muscles to tense (contract), which allows the body to move.
❑ Most people with spinal muscular atrophy are missing a piece of
the SMN1 gene, which impairs SMN protein production. A shortage of
SMN protein leads to motor neuron death, and as a result, signals are not
transmitted between the brain and muscles. Muscles cannot contract
without receiving signals from the brain, so many skeletal muscles become
weak and waste away, leading to the signs and symptoms of spinal muscular
atrophy.
 https://images.app.goo.gl/pFX9FF9usonkekGP7

❑ Spinal muscular atrophy is inherited in an autosomal recessive pattern, which means

both copies of the SMN1 gene in each cell have mutations. In most cases, the parents of
an individual with an autosomal recessive condition each carry one copy of the mutated
gene, but they typically do not show signs and symptoms of the condition.
❑ In rare cases, a person with spinal muscular atrophy inherits an SMN1 gene mutation
from one parent and acquires a new mutation in the other copy of the gene that occurs
during the formation of reproductive cells (eggs or sperm) or in early embryonic
development. In these cases, only one parent is a carrier of the SMN1 gene mutation.
❑ Individuals who have more than the usual two copies of the SMN2 gene usually do not
inherit the extra copies from a parent. They typically arise during a random error when
making new copies of DNA (replication) in an egg or sperm cell or just after fertilization.

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What Is Duchenne Muscular
Dystrophy?
❑ It affects the muscles, leading to muscle wasting
that gets worse over time.
❑ They occur primarily in males, though in rare
cases may affect females.
❑ It is caused by an alteration (mutation) in a gene,
called the DMD gene.
❑ It encodes for the muscle protein, dystrophin.
❑ Boys with Duchenne muscular dystrophy do not
make the dystrophin protein in their muscles.
❑ There is no known cure for DMD, there are
treatments that can help control symptoms.
 Progressive Muscle Weakness That Gets Early Signs May Include
Weakness Worse Over Time. Delayed Ability To Sit, Stand,
Or Walk And Difficulties
Enlarged Calf Muscles
Learning To Speak.
(Pseudohypertrophy)
(Increased size of calf SYMPTOMS
muscles) Using hands to get up off
the floor (Gower's
Loss (Atrophy) Of Both Most children with maneuver)
Skeletal And Heart DMD use a wheelchair
Muscle by their early teens.

Clinical Muscle Blood Genetic

DIAGNOSIS Diagnosis Biopsy Test Testing
❑ It is a progressive brain disorder that causes
uncontrolled movements, emotional problems,
and loss of thinking ability (cognition).
❑ Mutations in the HTT (HUNTINGTIN) gene
(nerve cells in the brain) cause Huntington
disease.
❑ The HTT mutation that causes Huntington
disease involves a DNA segment known as
a CAG (cytosine, adenine, and guanine)
trinucleotide repeat.
❑ It is an autosomal dominant
neurodegenerative disorder.
❑ The part of the brain most affected by HD is a
group of nerve cells at the base of the brain
known collectively as the basal ganglia.
❑ There is no treatment that can stop or reverse
the course of HD.
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Many people with Huntington disease

develop involuntary jerking or
twitching movements known as
chorea.
Tetrabenazine and deuterabenazine
can treat chorea associated with HD.

https://images.app.goo.gl/Qr7NyGFMdaK9nJ4Y6

Clinical Medical Genetic Brain Neurological &

Diagnosis History Testing Imaging Laboratory Tests.
❑ Multiple sclerosis (MS) is an autoimmune
disease that affects the brain and spinal cord
(central nervous system).
❑ MS affects women more than men.

❑ The disorder is most commonly diagnosed

between ages 20 to 40, but it can be seen at any
age.
❑ MS is caused by damage to the myelin sheath.
This sheath is the protective covering that
surrounds nerve cells. When this nerve covering
is damaged, nerve signals slow or stop.
❑ There is no known cure for MS at this time,
but there are treatments that may slow the
disease. The goal of treatment is to stop
progression, control symptoms, and help you
maintain a normal quality of life.
 https://images.app.goo.gl/zSBs9uQp1G8TYGWb9

https://images.app.goo.gl/VykHLy9KwJQvw2AP6 https://images.app.goo.gl/mLKWVZg4NYH1542y5 https://medlineplus.gov/ency/images/ency/fullsize/19238.jpg

❑ It is a rare neurological disease that primarily affects the nerve cells (neurons)
responsible for controlling voluntary muscle movement .
❑ More men than women get it.

❑ It is known as motor neuron diseases and caused by gradual deterioration

(degeneration) and death of motor neurons.
❑ The cause of ALS is not known, and scientists do not yet know why ALS strikes some
people and not others. However, scientific evidence suggests that both genetics and
environment play a role in motor neuron degeneration and the development of ALS,
❑ About 25 to 40 percent of all familial cases (sporadic cases) are caused by a defect in
the C9ORF72 gene (which makes a protein that is found in motor neurons and nerve
cells in the brain).
❑ 12 to 20 percent of familial cases result from mutations in the SOD1 gene that is
involved in production of the enzyme copper-zinc superoxide dismutase 1.
❑ There is no cure for ALS and no effective treatment to halt or reverse the progression
of the disease.
❑ Most people with ALS die from respiratory failure, usually within 3 to 5 years from
when the symptoms first appear. However, about 10 percent of people with ALS
survive for 10 or more years.
 FIGURE:
(A) Proximal and symmetrical upper limb
wasting results in an inability to lift arms
against gravity.
(B) The scapular spine, indicating wasting of
supraspinatus and infraspinatus muscles, as
well as substantial loss of deltoid muscle.
(C) Disproportionate wasting of the thenar
muscles combined with the first dorsal
interossei, the so-called “split-hand”, is a
typical feature in ALS.
(D) Substantial wasting of the tongue
muscles in bulbar-onset ALS.
https://images.app.goo.gl/3636EYov5PQWbkpo6
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cdn.jbs.elsevierhealth.com/cms/attachment/53fd47ef-
• Moving, swallowing (called dysphagia), Speaking or forming 51e8-4a4d-acd4-a3e55cab2dac/gr1.jpg

words (dysarthria), and breathing (dyspnea).

Electromyography Nerve Conduction Magnetic Resonance Blood and Muscle

(EMG) Study (NCS) Imaging (MRI) urine tests Biopsy
 https://images.app.goo.gl/kKFt3L5o6jxou2cBA

Neuropathy is damage or dysfunction of one or more

nerves that typically results in numbness, tingling,
muscle weakness and pain in the affected area.

▪ Nerve signaling in neuropathy is disrupted in

three ways:
1. loss of signals normally sent (like a broken
wire).
2. inappropriate signaling when there shouldn’t
be any (like static on a telephone line).
3. errors that distort the messages being sent
(like a wavy television picture).
 How is Neuropathy diagnosed?
❑ History and physical exam
❑ Neurologic exam
❑ Blood work and imaging tests (Magnetic resonance imaging
(MRI)
❑ Genetic testing
❑ Nerve conduction study (NCS)
❑ Tissue biopsies

TREATMENT:
❑ Some cases of neuropathy can be easily treated and
sometimes cured.
https://images.app.goo.gl/YWVim74kNdidg5nH7
❑ Not all neuropathies can be cured.
▪ Parkinson disease: MedlinePlus Genetics. (n.d.). https://medlineplus.gov/genetics/condition/parkinson-disease/#synonyms

▪ Parkinson’s Disease. (n.d.). National Institute on Aging. https://www.nia.nih.gov/health/parkinsons-disease

▪ Parkinson’s Disease. (n.d.). PD | MedlinePlus. https://medlineplus.gov/parkinsonsdisease.html

▪ Spinal muscular atrophy | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. (n.d.).
https://rarediseases.info.nih.gov/diseases/7674/spinal-muscular-atrophy
▪ Spinal muscular atrophy: MedlinePlus Genetics. (n.d.). https://medlineplus.gov/genetics/condition/spinal-muscular-atrophy/#inheritance

▪ NHGRI. About Duchenne Muscular Dystrophy. Genome.Gov. https://www.genome.gov/Genetic-Disorders/Duchenne-Muscular-Dystrophy

▪ Duchenne muscular dystrophy | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. (n.d.).
https://rarediseases.info.nih.gov/diseases/6291/duchenne-muscular-dystrophy
▪ Huntington disease: MedlinePlus Genetics. (n.d.). https://medlineplus.gov/genetics/condition/huntington-disease/

▪ Huntington’s Disease Information Page | National Institute of Neurological Disorders and Stroke. (n.d.). https://www.ninds.nih.gov/Disorders/All-
Disorders/Huntingtons-Disease-Information-Page
▪ The Basic Neurobiology of Huntington’s Disease (Text and Audio) – HOPES Huntington's Disease Information. (n.d.). HOPES Huntington’s Disease
Information. https://hopes.stanford.edu/the-basic-neurobiology-of-huntingtons-disease-text-and-audio/
▪ Basal Ganglia (Section 3, Chapter 4) Neuroscience Online: An Electronic Textbook for the Neurosciences | Department of Neurobiology and Anatomy - The
University of Texas Medical School at Houston. (n.d.). https://nba.uth.tmc.edu/neuroscience/m/s3/chapter04.html
▪ Multiple sclerosis. (n.d.). https://medlineplus.gov/ency/article/000737.htm

▪ Dr. Stephen Hawking: A Case Study on Using Technology to Communicate with the World | AccessComputing. (n.d.).
https://www.washington.edu/accesscomputing/dr-stephen-hawking-case-study-using-technology-communicate-world
▪ Amyotrophic Lateral Sclerosis (ALS) Fact Sheet | National Institute of Neurological Disorders and Stroke. (n.d.)
.https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Amyotrophic-Lateral-Sclerosis-ALS-Fact-Sheet
▪ Amyotrophic Lateral Sclerosis. (n.d.). ALS | Lou Gehrig’s Disease | MedlinePlus. https://medlineplus.gov/amyotrophiclateralsclerosis.html

▪ Peripheral Neuropathy Fact Sheet | National Institute of Neurological Disorders and Stroke. (n.d.). https://www.ninds.nih.gov/Disorders/Patient-
Caregiver-Education/Fact-Sheets/Peripheral-Neuropathy-Fact-Sheet
▪ Neuropathy (Peripheral Neuropathy). (n.d.). Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/14737-neuropathy