Recognizing Symptoms and Warning Signs

While every person’s journey with MPAN is different, the condition follows a general pattern of progressive changes in movement, vision, and thinking. Because MPAN typically moves slowly, it is important to distinguish between the expected progression of the disease and “red flag” symptoms that require immediate medical attention ^[1].

Early Motor Symptoms

Movement challenges are often the first sign of MPAN. In a large retrospective study of 85 patients tracking symptoms over time, nearly everyone (99%) experienced gait disturbances, or trouble walking, as a symptom ^[1].

• Pyramidal Signs: Affecting 95% of patients in the cohort study, these are signs of damage to the brain’s motor pathways. They include spasticity (muscle stiffness), weakness, and exaggerated reflexes ^[1][2].
• Dysarthria: This is an impairment of motor control of speech, which can include slurring or slowing. While it eventually affects about 90% of patients in the cohort study, it often appears later in the disease course than walking difficulties ^[1].
• Muscle Atrophy: Some patients develop motor axonal neuropathy, where the nerves connecting the spine to the muscles are damaged, leading to visible muscle thinning or “wasting” ^[3][4].

Visual Manifestations

Vision loss is a hallmark of MPAN, affecting roughly 82% of patients in the cohort study ^[1]. This is usually caused by optic atrophy, a condition where the optic nerve—the cable connecting the eye to the brain—becomes thin and pale ^[5].

Unlike some other eye conditions, this typically does not involve the retina itself. Doctors may use Optical Coherence Tomography (OCT) to measure this thinning or Visual Evoked Potentials (VEP) to see how quickly signals travel from the eyes to the brain ^[5]. You may notice your child or yourself having more difficulty seeing in low light or failing to notice things in the periphery.

Cognitive and Psychiatric Symptoms

As MPAN progresses, it can affect the mind as well as the body. This is especially common in individuals whose symptoms began in adulthood ^[6].

• Cognitive Decline: This may start as subtle memory loss or difficulty with complex tasks, sometimes progressing to dementia ^[3][7].
• Psychiatric Changes: Some people experience significant mood or behavioral changes, including anxiety, depression, irritability, or social withdrawal ^[8][9]. In rare cases, these can be the very first symptoms noticed ^[1].

Distinguishing Routine Progression from Emergencies

Understanding what is “normal” for MPAN can help reduce anxiety and ensure you get help when it is truly needed.

Routine Progression (Monitor and Discuss at Next Visit)

These symptoms are expected to worsen gradually over years:

• Slowly Increasing Stiffness: A gradual increase in leg stiffness or a slow transition to using a walker or wheelchair ^[1].
• Gradual Speech Changes: Speech becoming slightly more difficult to understand over several months ^[1].
• Mild Balance Issues: Occasional stumbles that do not result in serious injury.

Call the Clinic Promptly

These represent acute complications that need urgent evaluation from your care team:

• Acute Dysphagia: A sudden inability to swallow, frequent choking, or a “wet” sounding voice during or after meals. This can lead to aspiration pneumonia (food or liquid entering the lungs) ^[10][11].
• Sudden Weakness or Falls: A rapid change in the ability to walk or stand over days rather than months.

Red Flags (Call Emergency Services)

These represent situations that need immediate emergency attention:

• Psychiatric Crisis: Sudden, severe agitation, hallucinations, or immediate thoughts of self-harm ^[8].
• Seizures: While not universal, epileptic seizures can occur in NBIA disorders. Any new loss of consciousness or rhythmic shaking that fails to stop after a few minutes or fails to recover consciousness is an emergency ^[12].
• Breathing Difficulty: New shortness of breath, inability to clear the airway, or a very weak cough ^[11].
• Stroke-like Symptoms: Sudden focal weakness or inability to speak.

Variability in Movement Disorders

Beyond stiffness, many patients develop other movement challenges:

• Dystonia: Involuntary muscle contractions that cause repetitive movements or twisting postures (e.g., a foot turning inward) ^[13].
• Parkinsonism: Symptoms similar to Parkinson’s disease, such as tremors, slowed movement (bradykinesia), and a stooped posture ^[2][3].

The prominence of these symptoms varies widely. Some patients may have severe dystonia while others experience mostly parkinsonism or spasticity ^[2]. Progress is being tracked through registries like TIRCON to better understand why these differences occur [NCT05522374].