ALS and Multiple Sclerosis: Similarities and Differences

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ALS and Multiple Sclerosis: Similarities and Differences
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MS vs. ALS differences

Both MS and ALS are disabling.

  • ALS (amyotrophic lateral sclerosis, Lou Gehrig’s disease) and MS (multiple sclerosis) are not the same disease. They sometimes are confused because they have some similarities. However, they have more differences than similarities.
  • MS is neurodegenerative disease that results in the destruction the protective coating (myelin sheath) on nerves of the CNS (central nervous system), which causes a faulty relay of instructions from the brain to the body. Many people may have mild symptoms for years with periods of remission. In contrast, ALS destroys the nerve cells (neurons) so that the body cannot communicate with the brain. Symptoms of ALS progress continually, and result in paralysis, and death a few years after the initial diagnosis.
  • The similarities between these two conditions are that both MS and ALS are so-called neurodegenerative diseases that affect the brain and spinal cord (central nervous system or CNS). Both affect the body's muscles and nerves.
  • ALS and MS have no known cure.

The symptoms and signs of MS vary from person to person. When people with MS do have symptoms they include vision disturbances blurred vision or eye pain; muscle spasms; tingling, numbness, and prickling pain; muscles spasms in the arms and legs; fatigue, dizziness, tremors, and sexual dysfunction.

Click for more signs and symptoms of MS »

What are the main differences between MS vs. ALS

  • Multiple sclerosis is an autoimmune disease, while ALS is hereditary in 1 10 people due to a mutated protein.
  • MS has more mental impairment and ALS has more physical impairment.
  • Late stage MS rarely is debilitating or fatal, while ALS is completely debilitating leading to paralysis and death.
  • The age of diagnosis of MS usually is between age 20 and 50; rarely, it can occur in children and teens.
  • MS is more common in women and ALS is more common in men.

Multiple sclerosis symptoms and signs

  • Numbness and tingling in the body
  • Vision problems
  • Sexual dysfunction
  • Bowel problems
  • Depression
  • Mood swings
  • Fatigue, often when warming up to exercise
  • Slowed or fuzzy memory (cognitive problems)
  • Mild problems walking
  • Periods with few symptoms followed by relapses

ALS (Lou Gehrig's disease symptoms and signs

  • Muscle cramps
  • Trips and falls easily
  • Clumsiness
  • Problems holding the head up

What kind of disease is multiple sclerosis? See Answer

What are the causes of MS vs. ALS?

ALS is not considered an autoimmune disease, although some researchers theorize that it might be, due in part, to a disorganized immune response. Hereditary factors such as genes are thought to play a significant role in some patients because about one of every 10 patients has inherited the disease.

However, nine of 10 patients seem to have a spontaneous mutation in their genes that causes production of an unusual protein (ubiquilin2) that is speculated to play a significant role in the cause of the disease. Scientists don't know what triggers the onset of ALS.

However, researchers suggest that a chemical imbalance (high levels of glutamate, a chemical messenger) also may play a role in causing the disease.

In addition, researchers have noticed that members of the military have a much higher rate of ALS than the non-military population, but the cause of this statistical finding is unknown.

MS is considered to be an autoimmune disease, although we do not know what triggers it. However, we know what occurs in the body.

The body perceives myelin (a substance that coats nerve cells that allows them to function optimally) as a foreign substance and begins to destroy it.

This results in intermittent and/or poor functionality of nerve cells in the brain and spinal cord, that in turn, cause MS symptoms.

Multiple Sclerosis (MS) Symptoms and Treatment See Slideshow

Do MS and ALS have the same risk factors?

Age is risk factor for both ALS and MS, but ALS usually is diagnosed in older individuals (aged about 40 to 70), with an average age of onset of 55. While MS is diagnosed in a younger population (aged 20 to 50).

ALS is more common in men by about 20%, while MS is about 2 to 3 times more ly to develop in women.
Heredity plays a significant role in some individuals that develop ALS (about 10%). MS is not considered to be a hereditary disease, but new data may modify this conclusion.

In addition, being a member of the military raises the risk (twice as ly) of developing ALS. However, military service is not considered a risk factor for MS.

If you have an identical twin with MS, there is a 30% chance for you to develop MS.

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How are MS vs. ALS diagnosed?

If the history, symptoms, and physical exam suggest that ALS is a possible diagnosis, the patient is usually referred to a neurologist and given an electromyogram (EMG) to test muscle and nerve function.

If these functions are not normal, an MRI of the spinal cord and brain is typically ordered. Some patients will also have a spinal tap and blood tests to help exclude other diseases. The diagnosis of ALS is by exclusion.

This means that ALS is diagnosed after other possible diseases have been ruled out. A neurology consultant specialist usually does this diagnosis.

The same methods are used to diagnose MS. Moreover, ALS, multiple sclerosis is a diagnosis of exclusion (proving that other conditions are not the cause of symptoms).

However, MS has two additional diagnostic components that most neurologists to diagnose MS.

The first is evidence of damage in the central nervous system in two separate areas (for example, MRI findings of damage in the brain, spinal cord, and/or optic nerve), and the evidence that the damage occurred at two different points in time.

Treatment options

Treatments for ALS cannot reverse the nerve damage, but they can only slow progression of disease. The US FDA has approved two drugs for the treatment of ALS-riluzole (Rilutek) and edaravone (Radicava).

MS treatment is not a cure for multiple sclerosis. Treatments may help speed recovery from an MS exacerbation of symptoms and may slow the progression of the disease. Although a few patients may have mild symptoms, and not require treatment.

Treatments for MS attacks can include corticosteroids and plasma exchange (plasmapheresis, in which the liquid portion of your blood is removed, treated, and returned to the body). For progressive recurrent MS, ocrelizumab (Ocrevus) is the only FDA-approved therapy.

There are a number of other drugs for relapsing-remitting MS that may be prescribed by a neurologist to help reduce symptoms.

Treatment protocols for ALS and MS are best determined by your individual situation. Treatments are best determined in consultation with your primary care physician and a consultant such as a neurologist.

What are treatments for symptoms of MS vs. ALS?

Treatments for ALS cannot reverse the nerve damage, but they can only slow progression of disease. The US FDA has approved two drugs for the treatment of ALS-riluzole (Rilutek) and edaravone (Radicava).

MS treatment is not a cure for multiple sclerosis. Treatments may help speed recovery from an MS exacerbation of symptoms and may slow the progression of the disease. Although a few patients may have mild symptoms, and not require treatment.

Treatments for MS attacks can include corticosteroids and plasma exchange (plasmapheresis, in which the liquid portion of your blood is removed, treated, and returned to the body). For progressive recurrent MS, ocrelizumab (Ocrevus) is the only FDA-approved therapy.

There are a number of other drugs for relapsing-remitting MS that may be prescribed by a neurologist to help reduce symptoms.

Treatment protocols for ALS and MS are best determined by your individual situation. Treatments are best determined in consultation with your primary care physician and a consultant such as a neurologist.

Is there a cure for MS or ALS?

Currently, there is no cure for ALS or MS. However, in consultation with your primary care physician and a consultant (usually a neurologist), there are treatment protocols to help slow the progression of these diseases, and there are medications to reduce their symptoms.

What is the life expectancy for MS vs. ALS

In general, the prognosis for MS is much better than for ALS. People with MS may have a lifespan that is relatively normal, but is about six or seven years shorter than in those without the disease.

Depending upon the response to treatment and the presence of complications, the prognosis for MS patients may range from good to poor. In contrast, the life expectancy of a person with ALS is only about 2 to 5 years after the time of diagnosis, although about 20% may live somewhat longer than five years.

ALS progresses more rapidly than MS, and because nerve cells are the targets that become damaged, the prognosis is at best, fair to poor.

Medically Reviewed on 9/9/2019


National Multiple Sclerosis Society. “Diagnosing MS.” ALS Association. “Criteria for the Diagnosis of ALS.”


What’s the difference between ALS and MS?

ALS and Multiple Sclerosis: Similarities and Differences

Multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) are different diseases with some similar features and symptoms.

They both:

  • Affect your muscles and your ability to move your body
  • Attack your brain and spinal cord
  • Have “sclerosis” in their name
  • Cause scarring or hardening around nerve cells

They have some key differences, though. MS is an autoimmune disease that causes your body to attack itself. ALS, also called Lou Gehrig’s disease, is a nervous system disorder that wears away nerve cells in your brain and spinal cord. Both are treated differently.

“Sclerosis” comes from the Greek word for “scar.” Both ALS and MS cause scarring of the covering of nerve fibers. But the process of how that happens is different for each.

Nerve cells in your body are wrapped in thin coverings called myelin sheaths. They protect these cells, similar to how insulation protects electrical wires.

When you have MS, your body attacks the myelin sheaths in your brain and spinal cord.

When myelin sheaths are damaged, signals from your brain to other parts of your body get short-circuited.

ALS breaks down the actual nerve cells in your brain and spinal cord. These cells, called motor neurons, are in charge of the voluntary muscles in your arms, legs, face, and diaphragm for breathing.

You lose control of your motor functions, and as the motor neurons break down, the myelin sheaths harden.

In its early stages, some of the symptoms of ALS can be similar to those of MS. These include:

  • Stiff, weak muscles
  • Twitching or spasms
  • Fatigue
  • Trouble walking

If you’re having these symptoms, don’t try to guess what's going on. See a doctor and get a diagnosis.

As ALS attacks the nerves that deal with movement, your symptoms will get worse.

In the later stages of the disease, you can have:

Most people with ALS live 5 years or less after their diagnosis, but some live much longer. Research is underway to find treatments to extend and improve the quality of life.

With MS, the course of the disease is harder to predict. Your symptoms may come and go, and may even disappear for months or years at a time.

Un ALS, which affects only nerves involved in movement, MS can also affect your:

  • Senses — taste, smell, touch, sight
  • Bladder control
  • Mental and emotional health
  • Sensitivity to temperature

Because of complications related to the disease, the life expectancy of someone with MS is about 7 years less than someone without it, research suggests.

MS is diagnosed earlier in life than ALS.

  • It's usually discovered between the ages of 20 and 40.
  • ALS is often diagnosed between 40 and 70.

They affect genders differently.

  • More women than men get MS.
  • ALS is more common in men.

MS is most common in Caucasians. ALS affects all ethnic groups equally.

ALS can be inherited, but MS can't.

  • Up to 10% of ALS cases are passed down directly through genes.
  • That's not so with multiple sclerosis. But if your mom, dad, or sibling has MS, you’re at a higher risk of getting the disease.

More people in the United States have MS than ALS.

  • An estimated 12,000-30,000 people have ALS nationwide.
  • Approximately 1 million people are living with MS.

There's no cure for either condition, but treatments can help slow both diseases. Lifestyle changes can help you manage your symptoms and improve your quality of life, too.


Amyotrophic Lateral Sclerosis Society of Canada: “ALS, MS, and MD Fact Sheet.”

The ALS Association: “Ask the Doc: Q & A with Edward Kasarskis, MD, PhD.”

Johns Hopkins Medicine: “ALS – Amyotrophic Lateral Sclerosis,” “Multiple Sclerosis (MS).”

Multiple Sclerosis International Federation: “What is MS?”

National Institute of Neurological Disorders and Stroke: “Amyotrophic Lateral Sclerosis (ALS) Fact Sheet.”

National Multiple Sclerosis Society: “MS Symptoms,” “Summarizing Epidemiological Estimates,” “Estimating the Prevalence of MS,” “What Causes MS?”

Center for Diseases Control: “Prevalence of Amyotrophic Lateral Sclerosis – United States, 2010-2011.”

National MS Society: “MS the Disease.”

© 2019 WebMD, LLC. All rights reserved. Transverse Myelitis


Multiple Sclerosis vs ALS: What’s the Difference?

ALS and Multiple Sclerosis: Similarities and Differences

Multiple Sclerosis (MS) and Amyotrophic Lateral Sclerosis (ALS) – the latter of which is also known as Lou Gehrig's disease – are both neurodegenerative diseases. They share a handful of similarities, including some symptoms, but under the surface, they are very different conditions.

What is Multiple Sclerosis?

Multiple sclerosis (MS) is an autoimmune disease that attacks the fatty substance, called myelin, that forms protective covers around fibers (axons) of the central nervous system (CNS). This demyelination can lead to a range of symptoms relating to the CNS.

Because the CNS coordinates and influences both voluntary and involuntary activity all over the body, MS is extremely unpredictable, and the disease varies from person to person. Some of the most common symptoms include impaired cognitive abilities (memory, concentration, reasoning, problem-solving, etc.), fatigue, muscle weakness, spasms, numbness, tingling, and vision problems.

The ‘type’ of MS one lives with is defined by the way in which symptoms occur; some people experience distinct relapses (relapsing-remitting MS), others have a more progressive worsening of the disease (primary- and secondary-progressive MS). It is often argued that the types of MS are not truly independent of one another; rather, there is something of a spectrum upon which individuals fall. You can read more about the different types of MS here:

  • Multiple Sclerosis: What You Need to Know About the Different Types of MS

What is ALS?

Amyotrophic lateral sclerosis (ALS) is perhaps better known as Lou Gehrig’s disease in North America, named after the legendary baseball player who died of the disease in 1941.

ALS is a type of motor neuron disease (MND). Motor neurons, which are cells that control voluntary and involuntary muscle movements, are killed, preventing signals from reaching muscles and thus causing them to deteriorate (a process known as atrophy).

Upper motor neurons are in the brain, while lower motor neurons are in the spinal cord. “Classic” ALS is characterized by both upper and lower neurons deteriorating, and accounts for two-thirds of cases.

Other forms, with definitions from John Hopkins Medicine, are:

  • Primary Lateral Sclerosis (PLS) – a progressive neurological disease in which the upper motor neurons (nerve cells) deteriorate. If the lower motor neurons are not affected within two years, the disease usually remains a pure upper motor neuron disease. This is the rarest form of ALS.
  • Progressive Bulbar Palsy (PBP) – a condition that starts with difficulties in speaking, chewing and swallowing due to lower motor neuron (nerve cell) deterioration. This disorder affects about 25% of those with ALS.
  • Progressive Muscular Atrophy (PMA) – a progressive neurological disease in which the lower motor neurons (nerve cells) deteriorate. If the upper motor neurons are unaffected within two years, the disease usually remains a pure lower motor neuron disease.

Some people consider PLS, PBP, and PMA to be separate conditions from classic ALS, all of which can be classed as motor neuron diseases. Others consider them to be sub-types of ALS (in which case ALS and MND may be used interchangeably).

Symptoms can start in different parts of the body, depending on which motor neurons are damaged first. ALS progression usually follows a predictable pattern – the initial symptoms continue to worsen, and other body parts are eventually affected. In the latter stages, it leads to complete paralysis and respiratory failure.

ALS does not affect one’s senses, nor one’s intellectual reasoning.

Other posts you may be interested in on the MyTherapy blog:

Role of the Immune System

Multiple sclerosis is an autoimmune disease, meaning the immune system mistakenly attacks healthy cells within the body. The immune system seems to react to healthy cells as though they were antigens (foreign invaders from viruses, infections, etc.), creating autoantibodies to attack them.

In the case of MS, the myelin sheath is the target of the autoantibodies. In other autoimmune diseases, autoantibodies attack different cells (in the case of rheumatoid arthritis, for example, it is the tissue of the joints).

Un MS, amyotrophic lateral sclerosis is not considered an autoimmune disease.

There is evidence that neuroinflammation plays a role in its pathogenesis. Along with the activation of immune system cells in the brain (such as microglia and T-cells), this does suggest the immune system does play a role in the mechanisms and progression of ALS.

However, the precise nature of the immune system’s involvement is not well understood. At least one recent study even suggests that microglia actually protect motor neurons rather than contribute to their death.

The exact nature of ALS is not yet known, but there is no conclusive evidence to suggest the underlying mechanisms are similar to those of MS.

Risk Factors & Incidence

As is common when it comes to autoimmune diseases, women are around three times lier to develop multiple sclerosis than men are. It is usually diagnosed between 20 and 50 years of age.

Amyotrophic lateral sclerosis, on the other hand, is more common in men and usually occurs later in life than MS, with an average age of onset of around 55 to 60 years old.

Mysteriously, military veterans are twice as ly to develop ALS than the general population. It’s not known why this is the case, although greater exposure to toxins, such as lead, is one theory. No such link exists with MS.

MS is more common than ALS. The incidence rate in the USA is between 57 and 78 cases per 100,000 people in the southern states, and between 110 and 140 per 100,000 in the northern states. This geographical discrepancy is not limited to the USA; around the globe, MS tends to be more prevalent in places farther from the equator.

This has led to the theory that a lack of vitamin D, the production of which is prompted by UVB radiation from sunlight, may contribute to the development of MS.

While incidence rates of ALS vary around the globe, no such geographical pattern has been identified, suggesting the environmental risk factors differ for the two conditions.

In the USA, there are roughly 5,000 diagnoses per year, with an incidence rate of around 2 in every 100,000 people. It is estimated that around 16,000 people in the USA live with the ALS at any given time.


While some of the early symptoms of multiple sclerosis and amyotrophic lateral sclerosis may be similar, most are markedly different.

Symptoms of MS that are not common to those with ALS include:

  • Numbness and tingling
  • Vision problems
  • Cognitive changes
  • Hearing loss
  • Bowel and bladder problems
  • Heat sensitivity

ALS, on the other hand, does not affect the nerves that control the senses, nor does it usually cause bladder problems. Rather than having the mental impact MS does, ALS is a purely physical degenerative disease.

As the disease progresses, symptoms of ALS that are not common to MS include:

  • Difficulty breathing
  • Difficulty swallowing
  • Paralysis

Disease Course

Multiple sclerosis is completely unpredictable. Upon diagnosis, it is impossible to tell how the disease will progress or which symptoms are ly to occur.

Many people with relapsing-remitting MS, for example, will develop secondary-progressive MS – whereby relapses cease and, instead, symptoms gradually worsen – but how long this transition takes, if it happens at all, is unpredictable.

wise, while it is estimated that two-thirds of people with MS remain able to walk, there is no way to predict the long-term effect on mobility on a case-by-case basis.

MS is not usually fatal. Improved treatments have helped increase the life expectancy of people with MS, which is now estimated to be five to 10 years lower than the general population.

Amyotrophic lateral sclerosis is usually much more predictable. In the majority of cases, ALS is a rapidly progressing and fatal disease. Until treatment that can effectively slow, stop, or even reverse the progression of the disease is developed, most people live for around three to five years after their diagnosis.

Around 10% of people with ALS live for 10 years or longer after their diagnosis. Physicist, Stephen Hawking, lived with ALS for 55 years prior to his death in 2018, perhaps the longest anyone has ever lived with the condition.


The most obvious similarity between multiple sclerosis and amyotrophic lateral sclerosis is the shared use of the word ‘sclerosis’. Sclerosis, in medical terms, means hardening or stiffening of a structure.

When it comes to MS, sclerosis refers to the scars (or plaques/legions) that are caused by the damage done to the myelin sheath.

In ALS, lateral sclerosis refers to the stiffening of the lateral columns in the spine, which is a consequence of muscle being worn away.

Early Symptoms

Some of the early symptoms of ALS are similar to common MS symptoms, including:

  • Fatigue
  • Twitching & spasms
  • Trouble walking
  • Muscle pain
  • Muscle weakness and/or stiffness

As mentioned earlier, however, the symptoms become more diverse as each disease progresses.

Complex Genetic Disorders

nearly all (if not all) chronic diseases, genetics almost certainly play a key role in the development of MS and ALS. While some diseases, such as cystic fibrosis, are caused by a mutation to a single gene, both MS and ALS are polygenic. This means many genes have been associated with each condition.

Hundreds of genes have been identified as being more prevalent in people with MS than the general population.

It seems that the more of these genes you possess, the greater your risk of developing MS. As well as genetics, environmental and lifestyle factors – such as vitamin D deficiency and smoking – have been associated with an increased risk.

It is suspected that while the above factors may determine your risk, something else actually triggers the development of the disease. When it comes to MS, viruses (particularly human herpesviruses, such as Epstein-Barr virus) may well be the trigger, although the nature of the relationship is not fully understood.

Genetics, therefore, is just one component in an extremely complex process that leads to MS, making it impossible to predict whether you will actually develop either disease your genetic profile.

You can read more about the role of genetics in the development of MS here:

  • “Is Multiple Sclerosis Hereditary?” – The Role of Genetics in MS

Genetics also play a role in the development of ALS; 5% to 10% of cases are inherited (or familial). For the remaining cases, however, the cause is unknown.

Even in non-familial ALS, at least 25 different genes have thus far been associated with ALS. As is the case with MS, it is suspected that with each additional gene one carries, the slightly greater the risk of ALS becomes.

Other observations include the presence of a protein called ubiquilin 2, which may play a role, and high levels of a chemical called glutamate. There is evidence that glutamate may be one of the driving forces in the destruction of motor neurons.

However, quite how all of these elements combine to cause ALS remains unknown. MS, it is extremely complex puzzle, the genetic pieces to which complete only part of the picture.

No Cure

Perhaps more important than anything else written here, no cure yet exists for either MS or ALS.

Disease-modifying drugs for MS can help slow the progression of the disease, although such drugs are not suitable for everyone, are not guaranteed to work, and can have severe side effects. Other treatments tend to focus on recovery from relapses and treating specific symptoms.

Two disease-modifying drugs to slow the progression of ALS have been approved in the USA. However, their effect is often modest at best and in many cases, treatment focuses on limiting the severity of symptoms and maintaining the best quality of life possible for as long as possible.

Ultimately, each disease can have a devastating impact on those diagnosed and their loved ones.

As researchers uncover more information about MS and ALS, it can be hoped that more effective treatment options – and one day a cure – will be another similarity to add to the list.

Take a look at some of the other posts on the MyTherapy blog:


Concurrent multiple sclerosis and amyotrophic lateral sclerosis: where inflammation and neurodegeneration meet?

ALS and Multiple Sclerosis: Similarities and Differences

1Clinical Medical School, University of Oxford, Oxford, UK

Find articles by Grace Li

2Nuffield Department of Clinical Neurosciences (Neuropathology), University of Oxford, Oxford, UK

Find articles by Margaret M Esiri

2Nuffield Department of Clinical Neurosciences (Neuropathology), University of Oxford, Oxford, UK

Find articles by Olaf Ansorge

2Nuffield Department of Clinical Neurosciences (Neuropathology), University of Oxford, Oxford, UK

Find articles by Gabriele C DeLuca

Received 2011 Nov 18; Accepted 2012 Jan 24.

Copyright ©2012 Li et al; licensee BioMed Central Ltd.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The concurrence of multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) is exceedingly rare and the pathological features have not been examined extensively. Here we describe the key pathological features of a 40 year old man with pathologically confirmed concurrent MS and ALS.

This is the most pathologically illustrative case of coincident MS and ALS demonstrating inflammatory and neurodegenerative features characteristic of each disease, and is the first to exhibit the presence of TDP-43 inclusions in this clinical entity. The intricate relationship between neuroinflammation and neurodegeneration in these diseases is discussed.

Keywords: multiple sclerosis, amyotrophic lateral sclerosis, neuropathology, inflammation, neurodegeneration

MS has been traditionally viewed as an inflammatory demyelinating disease of the central nervous system with a secondary degenerative component whereas ALS has been considered a primary central and peripheral nervous system degenerative disorder with a secondary inflammatory component. In both diseases, neurological disability accrues secondary to axonal loss.

While they appear on opposite ends of the inflammatory/degenerative spectrum, the relationship between neuroinflammation and neurodegeneration is ly more dynamic and interactive than merely consequential as historically described.

Here we present a rare case of MS and ALS within the same patient and provide an overview of the complex interplay between neuroinflammation and neurodegeneration in these diseases.

A 37 year old man presented with a left VIth cranial nerve palsy and nystagmus that improved on a brief course of steroids. A diagnosis of possible MS was entertained.

Two years later, he experienced a subacute episode of bilateral leg weakness that was steroid responsive, prior to which he had a several month history of gradual decline in cognition, decreased visual acuity, widespread fasciculations with asymmetric upper limb weakness, and bilateral appendicular and truncal ataxia.

The subsequent 12 months were notable for the evolution of debilitating lethargy and fatigue, and progressive dysarthria and dysphagia. He died of respiratory compromise at the age of 40.

Formalin-fixed paraffin-embedded sections of pre-frontal and sub-frontal cortex, hippocampus, cerebellum, pons, low and high cervical and thoracic, lumbar and sacral spinal cord were stained with Luxol Fast Blue and Cresyl Violet (LBCV), Palmgren silver, Proteolipid protein (PLP), CD68 (PG-M1), CD3, and TDP-43 antibodies (Figure ​1). Using the LCBV stain, anterior horn cells (AHC) were identified quantified and compared to counts from two age- and sex-matched controls using established methods.

Pathological confirmation of MS was supported by evidence of multiple discrete areas of inflammatory demyelination in prototypic locations, including cortex (subpial, leukocortical), periventricular region, corpus callosum (Figure 1A, B), pons (Figures 1E, F), cerebellar peduncle, and lateral and posterior columns of the spinal cord (Figure ​1G).

Microscopically, lesions were characterized by infiltration of macrophages in the epicenter of acute lesions and the border of chronic active lesions (Figure ​1C); perivascular lymphocytic cuffing was noted in both (Figure ​1D). Lesions of all stages of demyelinating activity were observed, with acute lesions being predominant.

An extensive demyelinating lesion involving all layers of the hippocampus was the ly substrate for the patient's significant cognitive difficulty during life. Axonal density appeared to be mildly reduced in plaques when compared to surrounding normal appearing white matter.

Meningeal inflammation with monocytic infiltrates was observed often without underlying subpial demyelination. No evidence of TDP-43 inclusions were noted in any of the MS lesions studied.

There were several classic features of ALS pathology in areas distinct from MS plaques.

Ventral nerve roots were discoloured and selectively thinned (Figure ​1I), and a marked reduction (approximately 75%) of anterior horn cells at multiple serial lumbosacral cord levels when compared to controls was observed (Figure 1K, L).

Microglial activation was noted in i) layer V of the motor cortex (where Betz cells were sighted), and ii) at various levels of the spinal cord (Figure ​1H).

Corticospinal tract axonal loss appeared to be size selective, with large fibres particularly affected – a finding previously noted in ALS [1], and opposite to that found in MS (where small fibres are preferentially lost) [2]. Anterior horn cells in both cervical and lumbar cord demonstrated intracytoplasmic TDP-43 positive inclusions (Figure ​1M), with no evidence of such inclusions in the cortical and deep gray matter regions examined. FUS staining was negative in all areas studied.

Post-mortem confirmation of concomitant ALS with MS has been verified only three times previously in the literature. Hader et al.

[3] documented the case of a 56 year-old gentleman with a 27 year history of relapsing-remitting MS who, after 8 years of remission, developed bulbar signs with fasciculations, weakness and atrophy. Confavreaux et al.

[4] described a similar story of a 25 year-old female who presented with MS and after a 10 year quiescent period again developed a similar range of ALS- symptoms. Dynes et al.

[5] described a case of a 62-year lady presenting with progressive quadriplegia and bulbar palsy who also experienced symptoms consistent with Lhermitte's phenomenon and paresthesia within an overlapping timeframe of just several months. Here we present yet another case of pathologically confirmed coincident MS and ALS and highlight the emerging overlap between these respectively viewed inflammatory and neurodegenerative diseases.

Whether inflammation is a cause or effect of the primary pathology, similar immunological profiles have been observed in both diseases. Both innate and adaptive arms of the immune response have been implicated in the pathogenesis of MS.

Generalised activation of microglia, astrocytes and autoreactive T and B lymphocytes play a role in maintaining disease.

There is evidence for involvement of specifically the Th17 population in perpetuating inflammation, in particular in association with production of IL-12 [6].

Pro-inflammatory cell populations are important in ALS too. RT-PCR in ALS patients of spinal cord white and gray matter has shown increased glial expression of toll- receptor proteins [7].

Raised serum and CSF IL-12 and IL-17, levels in ALS patients, and high serum IL-23 levels point towards a similar cytokine and T-cell activation profile being present in both ALS and MS [8]. Increased levels of IL-13-producing T-cells correlate positively with ALS disease progression and severity.

Clinically, it is intriguing that cannabinoid-receptor antagonists, through their anti-inflammatory effects, have been shown to be efficacious in the symptomatic management of not only MS, but also of ALS [9].

Inflammatory cell populations need not always be detrimental to neuronal survival, sometimes conferring a degree of neuroprotection. Microglia produce neurotrophic factors which directly assist with regeneration, such as neurotrophin 3 and brain-derived neurotrophic factor.

There is recent evidence that activated T cell populations may also be crucial in neuroprotection, possibly in association with the secretion of IL-4 [10], associated with downstream production of insulin growth factor (IGF1).

These protective inflammatory mechanisms may be important in both MS and ALS.

Regardless of whether inflammation is a primary or secondary cause of pathology, the molecular basis of axonal loss in both diseases may converge on similar mechanisms.

Microglia and astrocytes are instrumental in ALS models; selective knock microglia in SOD1 mutant mice has been shown to delay disease onset and progression.

Glial cells are also hypothesised to amplify the degenerative process by activating NF-κβ by an inflammatory cytokine cascade, which incorporates the pro-apoptotic molecules FAS ligand and TDP-43 [11].

In the SOD1 models, nerve growth factor produced by activated astrocytes was associated with the death of motor neurons in the presence of NO and peroxide production [12]. Microglial cells may form part of a degradation pathway mediated by excitotoxicity as alterations in metabotropic glutamate receptor expression have been seen in human spinal cord [13].

Similar to ALS, MS pathology demonstrates activated microglia and astrocytes known to produce NO and reactive oxygen species. In MS, the presence of these reactive species may lead to degeneration of both the neuron and myelin sheath.

Secretion of IL-23 and osteopontin also leads to downstream production of TNF-α, promoting myelin degradation [6].

The activation of NF-κβ via an inflammatory cytokine cascade initiated and propagated by microglia and astrocytes has also been shown to occur in MS with the downstream consequence of neuronal/axonal degeneration.

Glutamate excitotoxicity is increasingly recognized as an important feature of both myelin and axonal destruction in MS, a feature which has prompted the use of anti-glutaminergic agents often used in ALS, such as riluzole, in experimental animal models of MS [14].

We present an unusual case of a pathologically confirmed coincident MS and ALS. Axonal loss, the substrate for irreversible neurological disability, is a shared pathologic feature in both conditions with intriguing similarities emerging in the molecular and cellular pathways leading to axonal demise.

Given the underwhelming impact of current therapies to prevent disability in MS and ALS, efforts directed at understanding the complex interplay between inflammation and degeneration in both MS and ALS will be essential to develop therapies designed to halt the devastating consequences of these diseases.

Consent for use of archival post-mortem tissue prior to 2006 is given for research activity on tissue at the Thomas Willis Oxford Brain Collection where no explicit objection for research use is given by the patient or next of kin (as in the case of this patient report) according to regulations outlined in the UK Human Tissue Act.

MS: multiple sclerosis; ALS: amyotrophic lateral sclerosis; TDP-43: TAR DNA-binding protein 43; IL: interleukin; IGF: insulin growth factor; SOD: superoxide dismutase; NO: nitric oxide; TNF: tumour necrosis factor.

The authors declare that they have no competing interests.

GD and MME conceived the design of the study. GL and GD acquired, analysed, and interpreted the data and drafted the manuscript. GD, OA, and MME revised the manuscript critically for important intellectual content and gave final approval of the version to be published. All authors read and approved the final manuscript.

GCD is supported by the AANF/CMSC John F. Kurtzke Clinician-Scientist Development Award and a Goodger Scholarship (University of Oxford), and MME and GCD receive support from the NIHR Biomedical Research Centre, Oxford.

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Similarities and Differences Between Multiple Sclerosis and ALS

ALS and Multiple Sclerosis: Similarities and Differences

Multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, are lifelong neurological diseases associated with muscle weakness and physical disability. Though they have similar sounding names, there are major differences between the two.

MS is not life-threatening, and life expectancy can be the same as that of anyone without the disease. ALS, on the other hand, requires major life-sustaining interventions and is eventually fatal.

While neither is curable, there has been major progress in terms of medical care and treatment for both conditions.

Neurological symptoms are the hallmark of MS and ALS, and while there are a few overlaps in symptoms, there are major differences.

Muscle weakness or trouble speaking (dysarthria) or swallowing (dysphagia) are among the first symptoms of ALS. In contrast, the first symptoms of MS are often paresthesias (numbness or tingling in extremities) or vision changes.

But either of these conditions can begin with mild problems, such as twitching of the hand, or a major event, such as leg weakness and a sudden fall.

ALS is characterized by a steady decline and worsening symptoms. In contrast, some types of MS are characterized by a gradual decline, while others are characterized by periods of remission (improvement) and exacerbations (relapses). 

Muscle Weakness (Arms and Legs)YesYes
Trouble SpeakingYesYes (less severe)
Cognitive IssuesYes (less common)Yes
Mood ChangesYes (less common)Yes
Swallowing ProblemsYesYes (less severe)
Breathing ProblemsYesRare
Vision ChangesNoYes
Sensory IssuesRareYes
Bladder/Bowel IssuesYesYes

ALS always advances to cause muscle paralysis (complete weakness). The muscles eventually atrophy (shrink and deteriorate). Eventually, everyone who has ALS will need an assistive device, such as a walker, wheelchair, or scooter.

Many people with MS experience mild or moderate muscle weakness, but only rarely experience paralysis. MS can affect your walking, and you may need an assistive device to get around, but most people with MS have more independence than those with ALS.

Dysarthria is common in ALS and MS. Dysarthria does not affect your understanding of words because it is not a language disorder. Your speech may be hard to understand, and you might also drool, especially when speaking.

Generally, dysarthria is more severe with ALS than with MS.

MS can produce cognitive dysfunction, which often manifests with clouded thinking or slowed thinking. This can be intermittent or can progress throughout the disease course.

ALS can also have cognitive and behavioral dysfunction that is worse with advancing disease, but not as common when compared to MS patients.

MS may produce mood and personality changes due to its direct effect on the brain.

ALS can also be associated with depression, anxiety, and personality changes, but these tend to be less common in patients with MS.

ALS commonly produces dysphagia. This will often progress to the point that a feeding tube or other means of nutrition is needed.

While MS-related swallowing problems can occur too, they are usually less severe and can typically be managed with swallowing therapy and dietary adjustments.

ALS usually causes impaired breathing due to degeneration of the nerves that power the respiratory muscles. Most people with ALS need a device to help with breathing, often starting with noninvasive ventilation (a mask that delivers oxygen), and then progressing to mechanical ventilation, which uses a powered machine to support lung function. 

Breathing problems rarely occur in MS and are usually mild. It is rare for MS-related respiratory problems to require breathing assistance.

In MS, vision can be affected by optic neuritis or nystagmus. In fact, decreased vision, double vision, and blurred vision are common in MS and often impact driving ability.

ALS does not affect vision, but it can cause altered eye movements late in the course of the disease.

Sensory changes are common in MS and can manifest with a range of unpleasant sensations, such as numbness and tingling or pain.

Some people with ALS report tingling sensations. However, this is not common and it usually goes away.

Tingling or sensory discomfort in ALS is caused by pressure and prolonged immobility rather than by the disease itself.

It is estimated that over 90 percent of people who have MS experience bladder dysfunction, including the inability to initiate urine and/or incontinence. People who have ALS can lose motor control and may experience bowel and bladder incontinence.

MS and ALS are both commonly associated with constipation.

Both of these conditions affect the brain and the spine.

However, in MS, demyelinating lesions can be seen in the brain and spine by MRI, while in ALS the neuronal damage is not able to be seen on imaging.

MS, but not ALS, can also involve the optic nerves (the nerves that control vision). In addition, the disease pathophysiology (biological changes) of the two conditions is completely different.

MS is a disease caused by demyelination of nerves in the brain, spine, and optic nerves. Myelin is a fatty coating that insulates nerves, allowing them to function efficiently. The nerves don't function as well as they should when they lack adequate myelin, and this results in the symptoms of MS.

Myelin is regularly replaced, and you can recover from a relapse without any residual effects. Sometimes, nerve damage or scarring can occur, and the neurological deficit can be long lasting or permanent.

It is believed that the demyelination of MS is caused by an autoimmune reaction, in which the body attacks its own myelin. There may be hereditary and environmental components to MS, but the cause remains a mystery.

With ALS, the motor neurons and its tracts (corticospinal and corticobulbar) located in the brain, brainstem, and spinal cord are gradually damaged, causing muscle weakness and atrophy (shrinkage). ALS is not believed to have an autoimmune cause, but it isn't clear exactly why the disease occurs.

Your physical examination can show some overlapping features. For example:

  • Both MS and ALS can cause you to have increased reflexes.
  • You may have decreased motor strength with either condition.
  • They can both affect one or both sides of your body.
  • Your muscle tone can be increased or decreased with either condition.

With MS, you can have altered sensation anywhere on your body (although you might not), but your sensory examination should be normal with ALS.

ALS is often characterized by muscle fasciculations, which look rapid fluttering of tiny muscles on your tongue, lips, or any other area of the body. With MS, you can have muscle spasms, which are noticeable, involuntary muscle jerks. Spasms may develop late in the course of ALS.

Because of this, testing is needed. You may have some of the same diagnostic tests if you have either of these two conditions, but the results will be completely different.

Your diagnostic tests can help distinguish these two conditions. MS is characterized by abnormalities that can be seen on a brain or spine magnetic resonance imaging (MRI) test, while these tests are not affected by ALS.

ALS is characterized by alterations in the patterns seen on electromyography (EMG), while MS patients have a normal study.

And, if you have a lumbar puncture (spinal tap), the results can show a characteristic pattern with MS that is not seen with ALS.

The treatment of the conditions is quite different, but both diseases are treated with disease-modifying therapy as well as therapy aimed at managing health complications.

MS disease-modifying therapies (DMTs) are taken on a regular basis to prevent exacerbations and overall neurological decline. There are also treatments used during an MS exacerbation, including corticosteroids.

A new disease-modifying therapy for ALS, Radicava (edaravone), was approved by the U.S. Food and Drug Administration (FDA) in 2017. This medication is believed to prevent neurotoxic damage, preventing disease progression. Because it is relatively new, the impact on people who have ALS is not yet known.

With both of these conditions, support for medical complications and disabilities is a major part of medical care.

For example, you may benefit from physical therapy to optimize your swallowing and motor control. A supportive brace can help you walk or use your hands and arms. Prevention of bed sores, respiratory infections, and malnutrition is important, and strategies related to these issues may be worked into your care over time.

Adapting to bladder and bowel issues may be necessary, and medications used to prevent painful spasms may be helpful.

If you or a loved one are experiencing any neurological symptom, be sure to speak with your doctor. There are many neurological diseases, and while the thought of having one can seem daunting, know that many neurological diseases are quite manageable.

Getting a speedy diagnosis is your best chance of optimizing your recovery in the long term. And even for a serious condition ALS, recent advances in care have improved the average survival rate.