Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative condition that selectively damages motor neurons in the brain and spinal cord, leading to muscle weakness and atrophy. The disease affects both upper motor neurons in the brain and lower motor neurons extending into the body. ALS does not show up definitively on a single standard blood test, despite the extensive testing required for diagnosis. Blood work is primarily used as an important piece of the diagnostic puzzle to rule out other treatable conditions that mimic ALS symptoms.
The Primary Purpose of Blood Testing in Diagnosis
The main reason a neurologist orders a comprehensive panel of blood tests is to perform a differential diagnosis. This systematic process involves excluding other possible causes for the patient’s symptoms before confirming ALS. Conditions that imitate the initial signs of ALS, such as muscle weakness and atrophy, include various metabolic, inflammatory, and autoimmune disorders.
Blood tests are used to check for thyroid disorders or Vitamin B12 deficiency, both of which can cause neurological symptoms. Doctors also screen for heavy metal poisoning, such as lead or arsenic, which affects the nervous system. Additionally, blood work includes tests for specific antibodies to exclude treatable autoimmune diseases like myasthenia gravis or multifocal motor neuropathy. Systematically eliminating these other possibilities narrows the diagnostic focus toward a motor neuron disease.
Specific Blood Markers Related to ALS
While no single blood test confirms ALS, certain substances show changes that can support the diagnosis or offer prognostic information. Creatine Kinase (CK) is an enzyme released into the bloodstream when muscle tissue is damaged. In ALS patients, CK levels are often mildly elevated due to the muscle breakdown that occurs as motor neurons die.
A highly elevated CK level is more characteristic of primary muscle diseases, known as myopathies, rather than ALS. Approximately 30% to 60% of ALS patients have elevated CK, but the level rarely exceeds 1,000 U/L.
Researchers are closely studying neurofilament light chain (NfL), proteins that form the structural skeleton of nerve cells. When motor neurons are damaged in ALS, NfL leaks into the blood, where it can be measured. Elevated NfL levels reflect the extent of neuronal damage observed in people with ALS. Although not yet a standard diagnostic criterion, NfL is considered a promising biomarker for tracking disease progression and is being used in clinical trials.
How Doctors Confirm an ALS Diagnosis
Since blood tests are mainly exclusionary, the definitive diagnosis of ALS relies on a comprehensive clinical evaluation combined with specialized neurophysiological testing. The neurologist conducts a detailed physical exam to look for signs of both upper motor neuron involvement, such as spasticity and hyperreflexia, and lower motor neuron involvement, including muscle weakness, atrophy, and fasciculations.
The most critical diagnostic tools are Electromyography (EMG) and Nerve Conduction Studies (NCS). NCS measure the speed and strength of electrical signals in the nerves; in ALS, sensory nerves typically function normally while motor nerve signals are affected. The needle EMG assesses the electrical activity of the muscles, revealing signs of active denervation, which is the hallmark of lower motor neuron loss.
The combination of clinical presentation and these electrophysiological findings is mandatory for confirming the diagnosis according to established criteria. Magnetic Resonance Imaging (MRI) scans of the brain and spinal cord are often performed. MRI is used not to detect ALS, but to rule out structural conditions like tumors, spinal cord compression, or multiple sclerosis that could cause similar symptoms.