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Can ALS be misdiagnosed?

ALS is frustratingly difficult to diagnose. Consider these ALS misdiagnosis statistics:¹

In about 10% to 15% of the cases, patients initially diagnosed with ALS actually have another disease or condition instead (false positive).

Nearly 40% of people with ALS initially receive a false negative. They are initially told they have another disease before ultimately receiving the ALS diagnosis.

So why is it so hard to get it right?

No single definitive test for ALS

In the rare cases of familial ALS, genetic testing may be able to determine whether a gene mutation is linked to the disease. However, carrying a gene mutation on an ALS gene does not guarantee a person carrying the mutation will develop symptoms during their lifetime. In addition, there is no specific test to confirm sporadic ALS, the non-inherited version that accounts for roughly 90% of ALS cases. And there’s no single way — such as a blood test — to make a definitive diagnosis.

That means doctors must rule out other conditions, which can be challenging, especially if it is early as there may not be sufficient symptoms yet to rule out other diseases. Dozens of conditions can mimic ALS. Two of the most common are multiple sclerosis (MS) and Parkinson’s disease. Like ALS, they are neurodegenerative disorders and have some of the same symptoms. Fortunately, key differences allow neurologists to rule them out.

It becomes trickier when we look at motor neuron diseases.

Diseases that Mimic ALS

Diseases that mimic ALS include lyme disease, cervical myelopathy, myasthenia gravis, and several others.

Lyme Disease

Lyme disease can mimic ALS due to its neurological symptoms, particularly muscle weakness and fatigue. Additionally, Lyme disease can sometimes cause nerve damage and inflammation, leading to symptoms similar to ALS, such as muscle twitching and difficulty with coordination.

Cervical Myelopathy

Cervical myelopathy can mimic ALS because both conditions can lead to weakness, muscle atrophy, and difficulty with movement. In particular, cervical myelopathy can cause weakness and loss of function in the upper extremities, which may be mistaken for the initial symptoms of ALS.

Myasthenia Gravis

Myasthenia gravis can mimic ALS because both conditions involve muscle weakness and fatigue. However, in myasthenia gravis, the weakness tends to fluctuate and worsen with activity, whereas in ALS, weakness typically progresses steadily over time. Additionally, both conditions can affect muscles involved in speech and swallowing, leading to similar symptoms in these areas.

Vitamin B12 Deficiency

Vitamin B12 deficiency can mimic ALS, particularly in its presentation of weakness, numbness, and balance problems. Both conditions can affect the nervous system and lead to muscle weakness and neurological symptoms. However, vitamin B12 deficiency can often be corrected with supplementation, and symptoms may improve with treatment, whereas ALS is a progressive and incurable neurodegenerative disease.

Post-Polio Syndrome

Post-polio syndrome can mimic ALS due to its presentation of progressive muscle weakness and atrophy. Both conditions involve the degeneration of motor neurons, leading to muscle weakness and functional impairment. Additionally, both PPS and ALS can cause fatigue and difficulty with mobility. However, in PPS, symptoms typically progress more slowly and may stabilize or even improve with appropriate management, whereas ALS follows a relentlessly progressive course.

As we discussed in an earlier post, ALS is the most common motor neuron disease, but it’s far from the only one. Sometimes these other conditions are mistaken for ALS, and sometimes ALS is mistaken for one of these other conditions. All motor neuron diseases cause progressive muscle weakness. Some affect upper motor neurons, some affect lower motor neurons, and some, including ALS, affect both.^2,3,4

It makes sense, therefore, that these diseases could sometimes be mistaken for ALS.

It also makes sense that what’s initially diagnosed as another motor neuron disease is, in fact, ALS. Many experts believe some of these — including progressive bulbar palsy, progressive muscular atrophy and primary lateral sclerosis — are on the ALS spectrum. And indeed, many of these initial diagnoses turn out to be ALS.^5,6

Lyme disease: Similarities lead to misconceptions

Lyme disease, which is a bacterial infection, sometimes gets misdiagnosed as ALS. Like ALS, Lyme disease symptoms may include twitching, muscle cramps and weakness in the hands, legs, feet or ankles. This has led to the misconception that the two are related. They are not.⁷

In fact, Lyme disease can present a variety of symptoms that mimic many conditions, including chronic fatigue syndrome, fibromyalgia, Alzheimer’s disease, depression, insomnia, and autoimmune disorders such as MS.

And so many other conditions …

What else can be mistaken for ALS? Here are a few other examples:^8,9,10Ìý

• Cervical myelopathy results from compression of the spinal cord in the neck. Several conditions, including cervical spondylotic myelopathy, fall into this category. They have a much better prognosis than ALS.^11,12Ìý
• Spinobulbar muscular atrophy affects men in their forties and fifties. It typically causes weakness in the muscles controlling speech, the neck and limbs.
• Myasthenia gravis (MG) is a common neurodegenerative condition characterized in the early stages by difficulties in swallowing. The difference: ALS affects nerve cells that control muscle movement, while MG is caused by an error in the transmission of nerve impulses to muscles.¹³

Other conditions that can be confused with ALS include:

• Poliomyelitis and post-poliomyelitis
• Heavy metal poisoning
• Late-onset Tay-Sachs disease
• Hereditary spastic paraplegia
• Inclusion body myositis
• Multifocal motor neuropathy
• Thyrotoxic myopathy
• Vertebral disc herniation

Cancers that Mimic ALS

In addition to these other serious conditions, cancer scares can also be misdiagnosed as ALS. This includes:

Brain Tumors

Particularly those affecting the brainstem or other parts of the brain that control motor function, can present symptoms like ALS. This includes gliomas and metastatic tumors from other body parts.

Spinal Tumors

Tumors in the spinal cord can mimic ALS as they may cause progressive muscle weakness, similar to the muscle atrophy seen in ALS. These tumors can be either primary (originating in the spinal cord) or metastatic (spread from other parts of the body).

Lymphoma

These types of blood cancers can occasionally present with neurological symptoms that mimic ALS, due to infiltration of cancer cells into the nervous system or due to paraneoplastic phenomena.

Recognizing ALS Symptoms

ALS symptoms typically emerge gradually and worsen over time. While the disease can affect individuals differently, several hallmark signs indicate its presence:

Muscle Weakness

One of the earliest symptoms of ALS is muscle weakness, which often begins in the hands, arms, legs, or feet. Individuals may notice difficulty with tasks such as grasping objects, walking, or climbing stairs. Muscle weakness may progress rapidly or gradually, depending on the individual.

Muscle Twitching

Muscle twitching, also known as fasciculations, is another common symptom of ALS. These involuntary contractions can occur in any muscle group but are frequently observed in the arms, legs, or tongue. While muscle twitching is relatively common and can occur for various reasons, persistent twitching accompanied by other ALS symptoms warrants medical evaluation.

Difficulty Speaking or Swallowing

As ALS progresses, it can affect muscles involved in speech and swallowing. Individuals may experience slurred speech, difficulty articulating words, or trouble swallowing (dysphagia). These symptoms can significantly impact communication and nutrition, leading to additional challenges in daily life.

Muscle Cramps and Stiffness

Muscle cramps and stiffness are often reported by individuals with ALS. These sensations can range from mild discomfort to severe pain and may occur spontaneously or worsen with physical activity. While muscle cramps and stiffness are nonspecific symptoms, their persistence alongside other ALS signs should prompt further investigation.

Unintended Weight Loss

Unintended weight loss is a common consequence of ALS, primarily due to muscle wasting and difficulty swallowing. As the disease progresses, individuals may experience challenges maintaining a healthy weight despite adequate calorie intake. Monitoring weight changes can provide valuable insight into disease progression and nutritional needs.

Respiratory Symptoms

In advanced stages of ALS, respiratory muscles weaken, leading to breathing difficulties. Individuals may experience shortness of breath, shallow breathing, or respiratory infections. Respiratory symptoms require prompt medical attention and may necessitate interventions such as mechanical ventilation to support breathing.

Seeking Medical Evaluation

If you or someone you know is experiencing symptoms suggestive of ALS, seeking prompt medical evaluation is essential. While there is no cure for ALS, early diagnosis allows for timely intervention and the implementation of supportive therapies to enhance quality of life and manage symptoms.

During a medical evaluation, healthcare professionals may conduct a thorough physical examination, review medical history, and perform diagnostic tests such as electromyography (EMG) and nerve conduction studies to assess nerve and muscle function. Additionally, genetic testing may be recommended in some cases, as certain genetic mutations are associated with familial ALS.

Signs of ALS

Recognizing the following signs can prompt early medical evaluation and potentially aid in managing the condition:

Muscle Weakness: One of the hallmark signs of ALS is progressive muscle weakness. Initially, this weakness may be subtle and involve specific muscle groups, such as hands or legs. Over time, it can spread to other parts of the body, leading to difficulty with walking, lifting objects, or performing daily activities.

Muscle Twitching (Fasciculations): ALS often presents with muscle twitching or fasciculations, which are involuntary contractions of muscles. These twitches may be visible under the skin and can occur in various parts of the body, including the arms, legs, face, or tongue.

Muscle Cramps and Spasms: Individuals with ALS may experience muscle cramps and spasms, which can be painful and contribute to muscle stiffness.

Difficulty Speaking or Swallowing: ALS can affect the muscles involved in speech and swallowing, leading to changes in voice, slurred speech, or difficulty swallowing (dysphagia). This can result in choking or aspiration pneumonia if not managed properly.

Weakness in Limbs: Weakness and muscle atrophy (wasting) in the arms and legs are common in ALS. This weakness may manifest as difficulty with tasks such as buttoning shirts, gripping objects, or walking.

Fatigue: Persistent fatigue and tiredness are often reported by individuals with ALS. This fatigue may be related to the increased effort required for movement due to muscle weakness.

Muscle Stiffness (Spasticity): Some individuals with ALS may develop muscle stiffness or spasticity, characterized by increased muscle tone and resistance to movement. This can contribute to difficulties with mobility and muscle coordination.

Difficulty Breathing: As ALS progresses, weakness may affect the muscles involved in breathing, leading to shortness of breath, especially during physical exertion. In later stages, individuals may require assistance with breathing through the use of mechanical ventilation.

Emotional and Cognitive Changes: ALS can also impact cognitive function and emotional well-being. Some individuals may experience changes in memory, decision-making, and behavior, while others may develop symptoms of depression or anxiety.

Loss of Motor Control: As the disease advances, individuals with ALS may experience loss of voluntary muscle control, leading to difficulties with fine motor tasks such as writing, typing, or buttoning clothes.

It’s important to note that ALS is a complex disease with variable progression, and not all individuals will experience the same symptoms or in the same order. Early diagnosis and multidisciplinary care involving neurologists, physical therapists, speech therapists, and other healthcare professionals can help manage symptoms and improve quality of life for individuals living with ALS.

Getting the ALS diagnosis right

Accurate, timely diagnosis of ALS is important for an array of reasons, including the ability to receive interventional therapies or participate in clinical trials for new treatments. But on average, getting a correct ALS diagnosis takes about a year.^14,15

An ALS misdiagnosis, either a false positive or false negative, not only means delays in treatment, but misdiagnosed patients may also undergo unneeded, painful and even dangerous surgery or treatment for a condition they don’t have.

For the time being, the best approach for patients who may have ALS is to get a referral to a neurologist with experience in ALS. In the future, it may be easier to get a definitive diagnosis. Researchers, funded by ÃÛÌÒ´«Ã½, are focused on finding biomarkers that could lead to earlier diagnosis. To learn more, visit /research.

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Sources

1

2 NIH Motor Neuron Diseases Fact Sheet https://www.ninds.nih.gov/health-information/disorders/motor-neuron-diseases

3 Pathology of Motor Neuron Disorders: Definition, Etiology, Epidemiology Dec. 22, 2019

4 Motor Neuron Disease (MND): 7 Types, Causes, Symptoms & Treatment. WebMD

5 Amyotrophic Lateral Sclerosis (ALS) – Diseases | Muscular Dystrophy Association. Muscular Dystrophy Association https://www.mda.org/disease/amyotrophic-lateral-sclerosis

6. NIH Motor Neuron Diseases Fact Sheet op.cit.

7

8

9 Richards, D. and Morren, J. A. and Pioro, E. P.: Time to diagnosis and factors affecting diagnostic delay in amyotrophic lateral sclerosis. Journal of the Neurological Sciences 417 (2020)

10

11 Onder, H., Yildiz, F. Cervical Spondylotic Myelopathy Mimicking Amyotrophic Lateral Sclerosis. Journal of Neurology Research, North America, 6, Sep. 2016. >.

12 Storti, B. et al.: ALS Mimics due to Affection of the Cervical Spine: From Common Compressive Myelopathy to Rare CSF Epidural Collection. Case Reports in Neurology 13 (2021)

13.

14

15 Jacobson RD, Goutman SA, Callaghan BC. Pearls & Oy-sters: The importance of atypical features and tracking progression in patients misdiagnosed with ALS. Neurology. 2016;86(13):e136-e139. doi:10.1212/WNL.0000000000002522