The document provides an overview of motor neuron disease (MND), including what it is, who it affects, types, symptoms, causes, diagnosis, treatment and management. MND is a group of neurodegenerative diseases that causes motor neurons in the brain and spinal cord to degenerate and die, leading to progressive muscle weakness. There are four main types depending on which motor neurons are affected. While there is no cure, early diagnosis and multidisciplinary care can help manage symptoms and maximize quality of life for those living with MND. Raising awareness of MND is important for improving understanding and care of those impacted by the disease.

1. University Of Development Alternative (UODA)
Submitted By:
Shamima Nasrin Bithi
Id: 032182011
Batch: 54th
Semester: 10th
Department of Pharmacy(UODA)
Submitted To:
Dr Kallol Debnath
Associate Professor
Department of Pharmacy
University of Development
Alternative(UODA)
Submission Date: 23 July 2021

2. Assignment On:
“Motor Neuron Disease: Public Awareness
and an Overview.”

3. Table of Contents
1. Introduction
2. What is Motor Neuron Disease (MND)?
3. Who does MND affect?
4. Types of Motor Neuron Disease
5. Symptoms
6. What causes Motor Neuron Diseases?
7. Epidemiology of Motor Neuron Disease
8. Genetics of Motor Neuron Disease
9. Diagnosis of Motor Neuron Disease
10. Treatment for Motor Neuron Disease
11. Management of Symptoms
12. Prognosis
13. Statistics of MND
14. Motor Neuron Disease in Bangladesh
15. Why MND awareness is important?
16. MND Awareness Day
17. Research Progression
18. Conclusion
References

4. 1. Introduction:
1.1. General Discussion:
 Motor neurons are specialized nerve cells in the brain and
spinal cord which transmit the electrical signals to muscles for
the generation of movement. Two sorts of cells are required.
Simply it is like two switches in an electrical circuit.
 The upper motor neuron starts at the top of the brain in an
area called the motor cortex and travels down to the spinal
cord to connect at different levels with the cells known as
lower motor neurons. These cells in turn travel out of the
spinal cord (e.g. along our arms and legs) and connect to
muscle.
 If motor neurons are damaged or die, the main consequence is
difficulty with voluntary movement (the expression of thought
through action).

5.  The upper motor neurons
originate in the cerebral cortex
and travel down to the brain stem
or spinal cord
 The lower motor neurons begin in
the spinal cord and go on to
innervate (to supply with nerves)
muscles and glands throughout
the body.
 In motor neuron disease (MND),
motor neurons undergo
progressive degeneration and die.
Figure: Motor Neuron

6.  Although classified as a rare disease based on its prevalence,
MND in fact quite common. There are approximately 140,000
new cases diagnosed worldwide each year.
 Living with motor neuron disease is extremely challenging and
often a terrifying prospect for patients. Although there is
currently no cure for MND, an early diagnosis of the disease is
very important for better understanding for the patient about
what is happening. Delay in diagnosis will prevent the patient
from receiving the appropriate care, management and support
they require to manage their symptoms. This can cause them to
experience pain and suffering that may have been avoided.
 Through this assignment I am going to show an overview on
MND like its types, causes, symptoms, diagnosis etc. and also
will discuss why awareness is important for this disease.

7. 1.2. Objective of this
assignment:
• Know the disease and who it
affects
• What is known about the
causes
• Know how to help manage the
disease
• Importance of awareness

8. 2. What is Motor Neuron Disease (MND)?
 Motor Neuron Disease (MND) is the name given to the group of
diseases in which the motor neurons undergo degeneration and
die. It goes under the umbrella of conditions termed
neurodegenerative disorders. Motor neuron diseases cause the
nerves in the spine and brain to lose function over time.
 Normally, messages or signals from nerve cells in the brain (upper
motor neurons) are transmitted to nerve cells in the brain stem and
spinal cord (lower motor neurons) and from them to muscles in the
body. Upper motor neurons direct the lower motor neurons to
produce muscle movements.
 When the muscles cannot receive signals from the lower motor
neurons, they begin to weaken and shrink in size (muscle atrophy
or wasting). The muscles may also start to spontaneously twitch.
These twitches can be seen and felt below the surface of the skin.

9.  When the lower motor neurons cannot receive signals from the
upper motor neurons, it can cause muscle stiffness (spasticity)
and overactive reflexes. This can make voluntary movements
slow and difficult. Over time, individuals with MNDs may lose the
ability to walk or control other movements.
 MND is a slowly progressive disease in that it gets steadily worse
over time. MND causes increasing disability due to muscular
weakness, generally without mental impairment.

10. 3. Who does MND affect?
 MND occur in both adults and children. In children, MNDs
are typically due to specific gene mutations, as in spinal
muscular atrophy. Symptoms can be present at birth or
appear in early childhood.
 In adults, MNDs are more likely to be sporadic, meaning
the disease occurs with no family history. Symptoms
typically appear after age 50, though onset of disease may
occur at any age.
 It affects slightly more men than women.
 Most cases occur spontaneously though some are
hereditary (about 10%).

11. 4. Types of Motor Neuron Disease:
 MND takes several forms. For some people, the symptoms are
widespread from the onset. However MND usually begins by
affecting a single limb or aspect of motor function, becoming more
generalized as the disease progresses.
 The disease can be classified into four main types depending on the
pattern of motor neuron involvement and the part of the body
where the symptoms begin.
I. Amyotrophic lateral sclerosis (ALS):
• Both upper and lower motor neurons are affected
• Limb muscle weakness and wasting
o ALS is the most common type, characterized by muscle weakness
and stiffness, over-active reflexes and, in some cases, rapidly
changing emotions.

12. o Initially the limbs cease to work properly. The muscles of
speech, swallowing and breathing are usually also later
affected.
o ALS is the term commonly applied to MND in many parts of
the world.
II. Progressive bulbar palsy (PBP):
• Both upper and lower motor neurons are affected
• Speech and swallowing muscle weakness and wasting
When ALS begins in the muscles of speech and swallowing it is
designated PBP. PBP, mixed bulbar palsy and pseudo-bulbar palsy
involve the muscles of speech and swallowing. The nerves that
control these functions are located in the bulb (the lower part of
the brain), hence the term bulbar palsy (paralysis). The limb
muscles may also later be affected.

13. Table: The four main types of motor neuron disease

14. III. Progressive muscular atrophy (PMA):
• Lower motor neurons are affected
• Slower rates of progression and significantly longer survival
compared to ALS and PBP
PMA is characterized initially by lower motor neuron signs
resulting in more generalized muscle wasting and weakness,
absent reflexes, loss of weight and muscle twitching. PMA can be
the hardest form of MND to diagnose accurately. PMA may begin
in the arms (flail arm type) or the legs (flail leg type).
IV. Primary lateral sclerosis (PLS):
• Upper motor neurons are affected
• Very rare and diagnosis is often provisional

15. 5. Symptoms:
MND has three stages of symptoms — early, middle, and advanced.
I. Early stage signs and symptoms:
In the early stage, symptoms develop slowly. The symptoms will
depend on the type of MND a person has and which part of the body
it affects.
Typical symptoms begin in one of the following areas:
• the arms and legs
• the mouth
• the respiratory system
They include:
• a weakening grip, which makes it hard to pick up and hold things
• fatigue
• muscle pains, cramps, and twitches
• slurred speech

16. • weakness in the arms and legs
• clumsiness and stumbling
• difficulty swallowing
• trouble breathing or shortness of breath
• inappropriate emotional responses, such as laughing or crying
• weight loss, as muscles lose their mass
II. Middle stage signs and symptoms:
As the condition progresses, the early symptoms remain and become
more severe. People may also experience:
• muscle shrinkage
• difficulty moving
• joint pain
• drooling due to problems with swallowing
• uncontrollable yawning, which can lead to jaw pain
• changes in personality and emotional state
• difficulty breathing

17. • Studies suggest that up to 50% of people with ALS may experience
brain involvement, including memory and language problems.
• Around 12–15% of people with ALS may develop dementia
(impaired ability to remember, think, or make decisions that
interferes with doing everyday activities). Some people also
develop insomnia, anxiety, and depression.

18. III. Advanced stage signs and symptoms:
• Eventually, a person in the advanced stage of ALS will need help
to move, eat, or breathe, and the condition can become life-
threatening.
• Breathing problems are the most common cause of death for
gradual weakness in their breathing muscles.
MND does not usually affect:
• The senses – sight, hearing, smell, touch and taste
• The bladder and bowel, although mobility problems can make it
more difficult to get to the toilet. Reduced mobility may also cause
constipation (as movement helps the bowel to work).

19. 6. What causes Motor Neuron Diseases?
• The causes of motor neuron disease are not yet known, but
ongoing research throughout the world is looking for causes.
• There are many theories, including exposure to environmental
toxins and chemicals, infection by viral agents, immune mediated
damage, premature ageing of motor neurons and loss of growth
factors required to maintain motor neuron survival and genetic
susceptibility.
• Experts believe that around 10% of MNDs are hereditary. The
other 90% happen randomly.
• The exact causes are unclear, but the National Institute of
Neurological Diseases and Stroke (NINDS) note that genetic,
toxic, viral, and other environmental factors may play a role.
• There is no evidence that motor neuron disease is transmissible
from person to person.

20. 7. Epidemiology of Motor Neuron Disease:
• The incidence of MND across the world is unclear. A systematic review
suggests that the incidence in Europe is 2–3/100,000 with a prevalence
of 5–7/100,000 population, while the incidence of ALS in the United
States is approximately 3–5/100,000. It is unclear if the differences
across countries relate to the design of studies, the ability of patients to
receive medical attention or differences in defining MND.
• In the Western Pacific the incidence of ALS among the indigenous
Chamorros in Guam had occurred at rates 50 to 100 times that noted
elsewhere around the world. The incidence of Guamanian ALS has
dramatically dropped since World War II, and it is suspected that dietary
toxins present in cycad seed, which were used as a primary source of
dietary flour, along with a possible genetic predisposition, may have
been at least in part responsible for this phenomenon.
• Genetic susceptibility may have contributed to an increased incidence of
ALS in the Kii Peninsula of Japan, which also represents a well-known,
but poorly understood, ALS cluster.

21. 8. Genetics of Motor Neuron Disease:
The genetics of MND has become increasingly complex. The first MND
gene mutation—SOD1—was reported in 1993. There are now more
than twenty different genes known to cause ALS. The most common
genes are:
• SOD1—accounting for 10–20 percent of fALS (Familial ALS) and 1
percent of sALS (Sporadic ALS)
• C9orf72 hexanucleotide repeat—accounting for 40 percent of fALS in
many countries, but less than 10 percent in Asia, found in 10–20
percent of sporadic ALS in Europe
• TDP-43—accounting for 4 percent of fALS and less than 1 percent of
sALS
• FUS/TLS—accounting for 4 percent of fALS and rarer in sALS
• Ataxin 2—accounting for 4 percent of fALS and 1 percent of sALS
• VCP—accounting for 1–2 percent of fALS
The investigation of these genetic mutations is providing some insights
into mechanisms of motor neuron cell damage and death.

22. 9. Diagnosis of Motor Neuron Disease:
There are no specific tests to diagnose MND. Symptoms may vary among
individuals and, in the early stages, may be similar to those of other
diseases, making diagnosis difficult.
If a doctor suspects someone has MND, they will refer them to a
neurologist, who will take a medical history, do a thorough examination,
and may suggest other tests, such as:
• Blood and urine tests: These can help a doctor rule out other conditions
and detect any rise in creatinine kinase, a substance that muscles produce
when they break down.
• MRI brain scan: An MRI cannot detect an MND, but it can help rule out
other conditions, such as stroke, brain tumor, or unusual brain structures.
• Electromyography (EMG) and nerve conduction study (NCS): These two
tests, which may be considered an extension of the neurological
examination, are the most important. These tests, usually done together,
can identify the differences between muscles diseases and MND.

23. 10. Treatment for Motor Neuron Disease:
There is no cure or standard treatment for MND. Symptomatic and
supportive treatment can help people affected by these diseases be
more comfortable while maintaining their quality of life.
Multidisciplinary clinics, with specialists from neurology, physical therapy,
respiratory therapy, and social work are particularly important in the care
of individuals with MND.
Medication
• Riluzole: Riluzole is the first drug approved by the U.S. Food and Drug
Administration (FDA) to treat ALS. In clinical trials, people taking riluzole
lived about 10 percent longer when compared to those not taking the
drug. However, riluzole cannot reverse the damage already done to
motor neurons. Although it is not fully understood how the drug works,
riluzole has been shown to reduce the release of glutamate and to block
sodium channels. Both of these actions may provide protection against
damage to motor neurons. But for some patients it showed side effects
also.

24. • Edaravone: In 2017, the FDA approved the drug edaravone to treat ALS.
Edaravone, an antioxidant, slows down the decline of physical function and
prevents disease progression in people with ALS. However, the drug, which
is administrated intravenously, cannot restore function.
• Nusinersen: In 2016, the FDA approved the first drug to treat children and
adults with SMA (Spinal muscular atrophy). Nusinersen, an injection
medication, is a type of treatment called anti-sense oligonucleotide therapy
and works by increasing the SMN (survival motor neuron) protein necessary
for the muscles and nerves to work normally.
• Muscle relaxers: Drugs such as baclofen, tizanidine, and the
benzodiazepines may reduce muscle stiffness and help muscle spasms.
• Botulinum toxin: Injections of botulinum toxin may be used to treat muscle
stiffness by weakening overactive muscles. They also may be injected into
the salivary glands to stop drooling. Excessive saliva also can be treated with
medications such as amitriptyline, glycopyrrolate, and atropine.

25. Supportive therapies
• Physical therapy and rehabilitation: These therapies may help improve
posture, prevent joint immobility, and slow muscle weakness and
atrophy. Stretching and strengthening exercises may help reduce
stiffness, as well as increase range of motion and circulation. Some
individuals require additional therapy for speech, chewing, and
swallowing difficulties. Applying heat may relieve muscle pain. Assistive
devices such as supports or braces, orthotics, speech synthesizers, and
wheelchairs may help some people maintain independence.
• Proper nutrition and a balanced diet: These things are essential to
maintaining weight and strength. People who cannot chew or swallow
may require a feeding tube.
• Ventilators: Non-invasive positive pressure ventilation (NIPPV) at night
can prevent sleep apnea. Some individuals may also require assisted
ventilation during the day due to muscle weakness in the neck, throat,
and chest.

26. Complementary therapies
• Some people find that complementary therapies can help to
relieve symptoms and reduce stress. Although not a treatment or
cure for MND, this type of therapy can be used to ‘complement’
conventional treatments if used in combination.
• A wide variety of complementary therapies exist, such as
massage, acupuncture and reflexology. Some local specialist
palliative care services and hospices offer complementary
therapies, as well as other forms of support to improve quality of
life.

27. 11. Management of Symptoms:
Patients experience a wide range of disabling symptoms over the
course of their illness including dyspnea, weakness and atrophy,
muscle cramps, dysarthria, dysphagia, weight loss, pathological
laughter and crying (pseudo bulbar affect), drooling, pain, sleep
disturbance and constipation. Professional expertise required to assist
with management of these symptoms while providing comprehensive
care for the patient and support for family caregivers.

29. 12. Prognosis:
• Prognosis varies depending on the type
of MND and the age of onset. Motor
neuron disease is a severely life-
shortening condition for most people.
• Life expectancy for about half of those
with the condition is 3-5 years from the
start of symptoms. However, some
people may live for up to 10 years, and in
rarer circumstances even longer.
• Famous astrophysicist Stephen Hawking
is the rare case, who’s ALS was
diagnosed in 1963, had the disease for
55 years, the longest recorded time. He
died at the age of 76 in 2018.

30. 13. Statistics of MND:
• In 2016, globally, 330,918 individuals had a motor neuron disease.
• Motor neuron diseases have caused 926,090 (881,566–961,758) DALYs
(disability-adjusted life year) and 34,325 (33,051–35,364) deaths in 2016.
• The worldwide all-age prevalence was 4.5 (4.1–5.0) per 100,000
people, with an increase in age-standardized prevalence of 4.5% (3.4–
5.7) over the study period.
• The all-age incidence was 0.78 (95% UI 0.71–0.86) per 100,000 person-
years.
• No risk factor analyzed in GBD (Global Burden of Disease) showed an
association with motor neuron disease incidence.
• The largest age-standardized prevalence was in high SDI regions: high-
income North America (16.8, 95% UI 15.8–16.9), Australasia (14.7, 13.5–
16.1), and Western Europe (12.9, 11.7–14.1). However, the prevalence
and incidence were lower than expected based on SDI in high-income
Asia Pacific.

31. 14. Motor Neuron Disease in Bangladesh:
• From a systematic analysis article by Prof
Giancarlo Logroscino found that in 2016,
2851(2501-3272) people had motor
neuron disease in Bangladesh. It caused
146(104-240) deaths and 5726(4307-8582)
DALYs in Bangladesh.
• B. Debnath et al. conducted a research
on MND in Bangladesh. In their research,
they mentioned 5 cases studies. Through
this they concluded that Motor neuron
disorders appear to be a clinically
heterogeneous disorder.

32. • Dr Md Raknuzzaman, Dr Md Ahsan Habib conducted a
hospital based prospective cohort study in the Dept. of
Neurology, BSMMU, during the period of time Jan 2010 to Dec
2011. In this study among total 34 participants, the highest
41% (n=14) participants were from 41-50 years’ age group.
Male were 59% (n=20) and female were 41% (n=14). They
concluded that gender and age of the participants was
potential aspect regarding amyotrophic lateral sclerosis (ALS)
disease.
• In Bangladesh, MND is very rare and general people don’t
know about that disease. MND related treatment centers are
very rare. CRP is the only institution in Bangladesh where MND
patients can have their general therapies

33. 15. Why MND awareness is important?
• Awareness matters. Every week, at least 300-460 people are
diagnosed with MND globally. MND awareness leads to a greater
understanding of MND in the wider community, which in turn
helps to increase levels of support, funding, and research, to
benefit those living with MND.
• Living with motor neuron disease is extremely challenging and
often a terrifying prospect for patients.
• Early diagnosis is very important for MND. Awareness can help
through a better understanding for the patient about what is
happening.
• A delay in diagnosis will prevent the patient from receiving the
appropriate care, management and support they require to
manage their symptoms. This can cause them to experience pain
and suffering that may have been avoided.

34. 16. MND Awareness Day:
• June 21 every year is MND/ALS Global Awareness Day.
MND/ALS Associations across the world use the day to raise
awareness of the disease to the general public.
• The day is also used to express hope that one day there will be
a turning point in the search for cause, treatment and cure of
this disease.

35. 17. Research Progression:
Research is focused on creating new and better medicines and
identifying genetic mutations and other factors that may influence
the development of these diseases.
Stem cells
Scientists are developing a broad range of model systems in animals
and cells to investigate disease processes and expedite the testing of
potential therapies. Since stem cells have the ability to develop into
many different cell types, including motor neuron and support cells,
they could potentially repair the nerve damage caused by MNDs.
These strategies have shown promise in mouse models, and
scientists are currently investigating the safety of using stem cells to
treat diseases like ALS in human clinical trials.

36. In other studies, scientists are investigating human spinal cord-
derived stem cells to discover if these cells can help improve function
in people with ALS. Researchers also are studying autologous
mesenchymal stem cells secreting neurotropic factors (MSC-NTF) as
treatment for ALS. MSC-NTF are made from a person’s own bone
marrow cells and then injected into the cerebrospinal fluid.

37. Gene therapy
Scientists are testing the potential of gene therapy to halt motor
neuron destruction and slow disease progression in animal models of
SMA and inherited ALS. Small clinical trials of SMN gene replacement
therapy are now underway in individuals with SMA. Other gene
therapy trials are studying familial ALS. Scientists are using advanced
sequencing technologies to identify new gene mutations that are
associated with MNDs. These gene discoveries are providing new
insights into the cellular disease processes and possible intervention
points for therapy.
Drug interventions
Researchers are testing whether different drugs, agents, or
interventions are safe and effective in slowing the progression of
MNDs.

38. 18. Conclusion:
Motor neuron disease (MND) is a neurodegenerative fatal disease
with no specific treatment and cure. With improved understanding
of its pathogenesis and genetics and the availability of high
throughput drug screening technologies, research in stem cells and
gene therapy, it is hoped that MND will soon enter in a new
therapeutic era.

39. References:
1. https://www.physio-pedia.com/Motor_Neurone_Disease_MND
2. https://www.gmjournal.co.uk/
3. https://pharmaceutical-journal.com/article/ld/motor-neurone-
disease-management-of-common-symptoms
4. https://brainfoundation.org.au/disorders/motor-neurone-disease/
5. https://stemcellthailand.org/therapies/motor-neuron-disease-mnd/
6. chrome-extension://mhjfbmdgcfjbbpaeojofohoefgiehjai/index.html
7. https://www.mndnsw.asn.au/what-we-do/infoline.html
8. (Facts (Oxford England)) Kevin Talbot, Rachael Marsden - Motor
Neuron Disease _ the Facts-Oxford University Press_OUP Oxford
(2008)
9. Robert H. Blank, Jerome E. Kurent, David Oliver - Public Policy in
ALS_MND Care_ An International Perspective-Palgrave Macmillan
(2021)