Amyotrophic Lateral Sclerosis - How to Diagnose

ALS Diagnosis Guide: Clinical Signs, EMG, Imaging & Genetic Testing

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease which targets nerve cells that control muscle movement. ALS typically begins insidiously and progresses over months to years, leading to progressive motor disability and ultimately respiratory failure.

Nevertheless, since ALS has symptoms common to a wide range of neurological disorders, making a timely and correct diagnosis has become one of the most significant challenges. This article outlines the diagnostic approach to ALS, emphasising the importance of specialised testing and medical support.

What Triggers the Need for ALS Testing?

ALS usually starts with muscle weakness, twitching, or stiffness. When patients present with such symptoms, most especially when they are localised (such as in the hand or leg) and gradually get worse, neurologists start investigations to find out whether the cause is ALS or another neuromuscular disorder.

Warning signs are:

• Persistent muscle fasciculations (twitches)
• Muscle atrophy
• Progressive weakness without pain
• Difficulty speaking, swallowing, or breathing
   

Such nonspecific symptoms require a thorough work-up to distinguish between ALS and such disorders as multiple sclerosis, myasthenia gravis, or peripheral neuropathy.

Clinical Examination and History Review

Initial diagnosis of ALS encompasses a physical examination and an in-depth medical history. Neurologists assess:

• Upper motor neurone (UMN) signs: Enhanced deep tendon reflexes, spasticity, and pathological reflexes (e.g., Babinski sign)
• Lower motor neurone (LMN) signs: Fasciculations, muscle atrophy and weakness
• Pattern of progression: Symptom spreads throughout body parts, especially the mouth, limbs and trunk
• Speech and swallowing difficulties: Bulbar involvement is a key indicator.
   

Clinical assessment alone is not sufficient to diagnose ALS, but it can help direct additional testing by providing a restricted diagnostic focus.

Electromyography (EMG) and Nerve Conduction Studies

Electromyography (EMG) is one of the most important diagnostic tools for ALS. EMG assesses the electrical activity of muscles and can detect patterns consistent with motor neurone degeneration.

EMG findings across multiple regions support ALS when interpreted in conjunction with clinical upper and lower motor neurone signs and disease progression.

NCS, when done together with EMG, assesses the functioning of peripheral nerves and aids in the elimination of other possible conditions, such as neuropathies or demyelinating diseases.

Magnetic Resonance Imaging (MRI) to Rule Out Mimics

MRI is not used to confirm ALS but is essential to rule out structural conditions that mimic its symptoms, such as:

• Spinal cord compression
• Brainstem tumours
• Cervical spondylotic myelopathy
• Multiple sclerosis
   

Normal imaging results, when combined with clinical and EMG evidence, support an ALS diagnosis.

Blood and Laboratory Tests

To exclude treatable conditions that can resemble ALS, blood tests are typically conducted:

• Thyroid function tests
• Vitamin B12 and folate levels
• HIV and syphilis serologies
• Autoimmune markers (ANA, anti-GM1 antibodies)
• Heavy metal screening is considered only when exposure history or clinical suspicion exists. 

While none of these confirm ALS, they help eliminate alternative explanations for motor symptoms.

Lumbar Puncture and Cerebrospinal Fluid Analysis

Neurologists may perform a lumbar puncture in certain cases to examine the cerebrospinal fluid (CSF). This is often done to rule out:

• Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
• Multiple sclerosis
• Infections of the nervous system
   

A normal CSF profile, helps exclude inflammatory, infectious, or demyelinating disorders.

Revised El Escorial Criteria for ALS Diagnosis

Neurologists rely on the Revised El Escorial Criteria to formalise ALS diagnosis, which assesses the presence of upper and lower motor neurone signs across different body regions. ALS is categorised as:

• Definite ALS: Upper and lower motor neurone signs in at least three regions
• Probable ALS: Signs in at least two areas with some upper motor neurone findings
• Possible ALS: Signs confined to one region
   

This classification aids in both diagnosis and inclusion in clinical trials.

The Role of Genetic Testing

Approximately 5 to 10% of ALS cases are familial. Mutations in genes like C9ORF72, SOD1, and FUS are associated with familial ALS. While not routinely performed in all patients, it can help:

• Confirm diagnosis in familial cases
• Support future therapeutic decisions or trial eligibility
   

Assessing Functional Progression

Once ALS is diagnosed, measures like the ALS Functional Rating Scale-Revised (ALSFRS-R) and staging systems (King’s and MiToS) are used to assess disability level and progression. These tools guide therapeutic decisions and trial eligibility.

Why Early Diagnosis Matters

ALS progresses rapidly, and early diagnosis allows for:

• Timely intervention: Including the use of riluzole and edaravone to slow progression
• Nutritional and respiratory planning
• Access to clinical trials
• Psychological support and palliative care preparation
   

Furthermore, early confirmation empowers patients to make critical decisions about work, mobility aids, and long-term care.

Reader Information: This article is intended for general informational and educational purposes only. Diagnosis and management of amyotrophic lateral sclerosis (ALS) require evaluation by a trained neurologist and may vary based on individual clinical circumstances. 

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