Hello, everyone. I'm Dr. Bakri Alsheikh, and I will be discussing paramytonia congenita. This is an A&EM teachable moment. This is a case of a 64-year-old woman presenting with muscle stiffness and pain that started at the age of 7. She recalls during winter in elementary school, she could not unzip her coat without the teacher's help. And over the years, she had difficulties performing tasks that require repetitive activity, such as cutting a loaf of bread or pulling weeds in the garden. She said at times she will get weakness in the arms and hands, and that usually lasts for several minutes. She also said she learned to live with it, but things worsened after she moved from the West Coast to the Midwest area, which she attributes to the cold weather. She reported no similar history in the family. Her neurological examination revealed normal higher mental function and normal motor and sensory examination. She was told to close her eyes tightly and then quickly open them. Prior to seeing that video, it's worth noting also that she did not have any ptosis or atrophy of the temporal or masseter muscles. As you can see, she had minimal difficulty opening the eyes at first, but it became harder with repeated attempts. The overactivity of the frontalis muscle confirmed her efforts to open the eyes. Similarly, she could release a strong grip at first, but it became harder with subsequent attempts. These findings are consistent with paramyotonia, or paradoxical myotonia, which refers to a paradoxical response to exercise, unlike the warm-up phenomenon observed in other myotonic disorders, where repeated movements reduce the myotonia. In this video, there is delayed relaxation following percussion over the extensor muscles in the forearm. How should one approach patients with clinical myotonia? Let's start by defining myotonia. It is derived from the Greek word myo, which is muscle, tonia, which is tension. It is characterized by delayed relaxation of skeletal muscles after voluntary contraction or after percussion. From a practical point of view, patients with clinical myotonia belong to two groups, myotonic dystrophies, and these are characterized by progressive weakness and extra-muscular manifestations, including multi-system disorders, such as the heart, the lung, the gastrointestinal, as well as cognitive. The non-dystrophic myotonias, on the other hand, are characterized by exclusive skeletal muscle dysfunction in the absence of progressive weakness and atrophy. This group is further divided on the basis of the ion channel involved and clinical phenotype. Myotonia congenita is caused by loss-of-function mutation in the chloride channel, and it can be autosomal dominant, Thompson's disease, or recessive Becker's disease, with the latter having a more severe and earlier-onset phenotype. The other group is caused by gain-of-function mutations in the sodium channel, the SCN4A gene, and that can result in paramyotonia congenita or sodium-channel-related myotonias. The sodium-channel myotonias is further divided into subtypes based on the clinical features of fluctuation, permanent symptoms, and acetazolamide responsiveness into subtypes of myotonia fluctuants, myotonia permanents, and acetazolamide-responsive myotonia. Another example of SCN4A-related disorder, where weakness is the most prominent feature, but myotonia can occur in the hyperkalemic periodic paralysis, where myotonia is described in around 50% of the patients. Our patient diagnosis of paramyotonia congenita was confirmed on genetic testing. Paramyotonia congenita was first brought to light by Uhlenberg in the 19th century. It is inherited as an autosomal dominant disease, similar to other SCN4A-related disorders. The symptoms start in the first decade, and it is characterized by myotonia, which, as we alluded to earlier, is difficulty to relax muscles, and the myotonia in this particular disease worsens rather than improves by exercise. It's also aggravated by cold. The face and the arms are predominantly impacted, in contrast to patients with chloride-channel myotonias, where the legs are mostly involved. Patients frequently express pain and fatigue as prominent features. While a methodic weakness might occur, it tends to be brief, usually lasting seconds to minutes, but may last a day or two. Unlike patients with myotonic dystrophies, persistent muscle weakness is rare, and it's usually proximal and mild if it did occur. Most patients exhibit clinical paramyotonia or paradoxical myotonia, which is unique and reported to be close to 100% specific for SCN4A-related disorders. Percussion myotonia can be present. Muscle hypertrophy, usually a key feature in patients with myotonia congenita, can be seen in about a third of patients with paramyotonia congenita. The diagnosis is based on history and examination findings, the presence of electrical myotonia on EMG, and genetic confirmation. EMG reveals electrical myotonia in proximal and distal limb muscles. These are high-frequency spontaneous discharges with waxing and waning amplitude and frequency. Genetic testing is a gold standard. It's now routinely performed using next-generation sequences. In cases where genetic testing is unrevealing or shows variants of unknown significance, short exercise tests could be helpful. The short exercise test is conducted with a standard under-motor nerve conduction study recording setup. Baseline CMAP measurements are taken, followed by a maximum isometric contraction of the abductor digiti minimi muscle for 10 seconds, and the CMAP is recorded every 10 seconds for 1 minute. We're looking for a decrement, and an abnormal decrement is defined as a reduction in the amplitude and area exceeding 20%. In patients with paramyotonia congenita, one is expecting to see progressive CMAP decline is observed with repeated trials and exposure to cold. CK levels are usually normal or mildly elevated. There is an evolving role for muscle MRI, which can show T1-weighted changes indicative of fatty infiltration, and STIR hyperintensity changes reflective of calf muscle edema. There is currently no FDA-approved treatment, however symptomatic treatment using off-label medications that block the sodium channel are reported to be helpful. Some of these medications include maxillitine, lamitrigine, ranolazine, carpamezepine, and finitoin. Patients should avoid triggers whenever possible, such as exposure to cold. Additionally, the anesthetic sexenylcholine should be avoided as it can cause severe generalized muscle stiffness, also known as myotonic crisis. Physical therapy can also be beneficial, and it is important to note that there is typically a moderate worsening of symptoms over a patient's lifetime. If you are interested in reading more about this topic, here are additional references for the information provided.

paramyotonia congenita

muscle stiffness

sodium channel mutation

genetic testing

myotonic dystrophies