Periodic paralysis

Types

Periodic paralysis is an autosomal dominant myopathy with variable penetrance, meaning only one parent needs to carry the gene mutation, but not all family members are equally affected. Specific diseases include hypokalemic periodic paralysis, where potassium leaks into muscle cells from the bloodstream; hyperkalemic periodic paralysis, where potassium leaks out of cells into the bloodstream; and paramyotonia congenita, which often accompanies hyperkalemic periodic paralysis but may occur alone, with muscle contracture developing during exercise or activity and attacks possibly triggered by low potassium.

Andersen-Tawil syndrome includes significant heart rhythm problems, fainting, and risk of sudden death, with potassium levels possibly low, high, or normal during attacks; patients may also have skeletal abnormalities such as scoliosis, syndactyly, clinodactyly, micrognathia, and low-set ears. A patient must have another form of periodic paralysis to have Andersen-Tawil syndrome, and if they have hypo- or hyperkalemic periodic paralysis, they have a 50% chance of developing it if they carry the gene.

Cause

Periodic paralysis involves sudden episodes of muscle weakness linked to potassium levels in the blood. Common triggers include physical activity and eating carbohydrates. A key feature is that attacks occur after resting following exercise, unlike non-dystrophic myotonias. Mutations in the Nav1.4 sodium channel are a major cause.

In hyperkalemic PP, potassium levels often rise above 5 mM during an attack, though attacks can also happen without this increase. Weakness episodes are brief, lasting minutes to hours, and can occur up to ten times per month. Hypokalemic PP involves low potassium, sometimes dropping below 3 mM during attacks. These episodes last much longer than those in hyperkalemic PP and can be set off by stress, a high-sugar diet, or rest after exercise.

Diagnosis

Periodic paralysis is unusually difficult to diagnose, with patients often reporting years of wrong diagnosis and treatments that worsened their condition. Migraines occur in up to 50% of patients and can cause confusing symptoms including headaches, speech difficulties, and visual, auditory, or sensory auras. DNA testing is available for only about half a dozen common gene mutations, while dozens of known mutations are not routinely tested.

Electromyography findings are not specific, but the McManis Protocol, also called the Compound Muscle Amplitude Potential test (CMAP), can assist diagnosis when performed by a skilled neurologist. The old glucose/insulin provocative testing should not be used as it can cause life-threatening symptoms. Potassium levels do not have to be outside normal limits to cause serious paralysis; total body potassium is usually normal but in the wrong location.

Treatment

Treatment plans for periodic paralysis are customized based on the specific type. Options include carbonic anhydrase inhibitors like acetazolamide, potassium supplements with a potassium-sparing diuretic for hypokalemic forms, or potassium restriction and thiazide diuretics for hyperkalemic forms. Lifestyle changes, such as carefully managed activity levels, are also key. For Andersen-Tawil syndrome, a pacemaker or defibrillator may be needed for heart issues.

Did You Know?

• Disability from periodic paralysis can range from minor occasional weakness to permanent muscle damage requiring a powerchair.
• Most people with periodic paralysis function fairly well with drugs and lifestyle changes.