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.
The same, but different
Diseases that Mimic ALS
Diseases that mimic ALS include lyme disease, cervical myelopathy, myasthenia gravis, and several others.
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:8,9,10
- 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.11,12
- 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:
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.
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).
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.
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 Target ALS, are focused on finding biomarkers that could lead to earlier diagnosis. To learn more, visit https://www.targetals.org/research.
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 https://emedicine.medscape.com/article/2111360-overview
4 Motor Neuron Disease (MND): 7 Types, Causes, Symptoms & Treatment. WebMD www.webmd.com/brain/what-are-motor-neuron-diseases
5 Amyotrophic Lateral Sclerosis (ALS) – Diseases | Muscular Dystrophy Association. Muscular Dystrophy Association https://www.mda.org/disease/amyotrophic-lateral-sclerosis
- NIH Motor Neuron Diseases Fact Sheet op.cit.
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) https://www.sciencedirect.com/science/article/pii/S0022510X20303919
11 Onder, H., Yildiz, F. Cervical Spondylotic Myelopathy Mimicking Amyotrophic Lateral Sclerosis. Journal of Neurology Research, North America, 6, Sep. 2016. https://www.neurores.org/index.php/neurores/article/view/397/394>.
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)
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