Monomelic Amyotrophy

What Causes Monomelic Amyotrophy?

Scientists don’t the precise cause of MMA. However, one theory is that repeated neck movements cause nervous systems structures (the cervical dural sac or thecal sac) to shift and put pressure on sensitive nerve fibers in the spinal cord. This pressure could disrupt the transmission of nerve signals from the brain to the arms, resulting in muscle weakness or loss of function.

Other possible causes of MMA include:

• An autoimmune response that causes the body’s immune system to attack healthy cells inappropriately
• A reaction to an infection
• Exposure to toxins
• A genetic predisposition

Is Monomelic Amyotrophy Hereditary?

MMA is not thought to be an inherited disorder. In most cases, people with MMA do not have any family history of the condition, and scientists have not found any specific gene mutations that appear to be associated with MMA.

In a small number of cases, MMA has occurred in multiple members of the same family. This suggests that there may be a genetic link to the disorder. However, the condition likely results from a combination of genetic predisposition and external environmental factors.

How Is Monomelic Amyotrophy Detected?

Symptoms of MMA usually appear sometime between adolescence (age 14-15) and early adulthood (age 25). The first symptom is typically weakness in one arm and/or hand without associated pain. Early detection and treatment may help prevent the worsening of symptoms.

Several other disorders have similar early symptoms, and they must be ruled out before a diagnosis of MMA can be made. These disorders include:

• Poliomyelitis
• Multifocal motor neuropathy
• Syringomyelia
• Anterior interosseous nerve syndrome
• Ulnar neuropathy
• Cervical vertebral abnormalities
• Spinal cord tumors
• Brachial plexopathy

How Is Monomelic Amyotrophy Diagnosed?

A doctor may suspect MMA when a patient exhibits weakness in one arm, especially when symptoms begin during adolescence or early adulthood. The diagnostic process will focus on looking for the distinctive signs of MMA and excluding other possible causes.

Diagnostic steps may include:

• Assessment of the patient’s medical and family history
• Physical and neurological exams
• Imaging scans such as magnetic resonance imaging (MRI) or computerized tomography (CT) to look for compression or deterioration of nerve tissue in the spinal cord
• Nerve conduction tests to look for problems in the communication between the nervous system and the arm muscles

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is Monomelic Amyotrophy Treated?

MMA has no cure. Treatments aim to keep symptoms from getting worse and to improve muscle function. Common treatments and therapies include:

• Use of a neck brace (cervical collar) to prevent movement of the neck that may worsen symptoms
• Strength exercises
• Physical therapy
• Occupational therapy
• Monitoring for worsening symptoms

How Does Monomelic Amyotrophy Progress?

MMA symptoms may worsen over 3-9 years after they initially begin. After that, symptoms usually stabilize, although another period of worsening symptoms after age 40 has occurred in rare cases.

MMA is not fatal, and people with the condition usually do not experience severe long-term disabilities. However, in some cases, the function of one hand may be lost entirely.

How Is Monomelic Amyotrophy Prevented?

The cause of MMA remains unknown, and there is no known way to prevent the disorder.

Monomelic Amyotrophy Caregiver Tips

• MMA is a rare and not well-understood disease. If your child is experiencing symptoms of the disorder, you may have to be an advocate for their medical treatment. Learn all you can about MMA and ask essential questions about the medical professionals treating your child.

Monomelic Amyotrophy Brain Science

MMA is a disorder of the lower motor neurons. These nerve cells are part of the peripheral nervous system, a network of nerves that connect the central nervous system (the brain and spinal cord) to the rest of the body. Lower motor neurons are connected to the brain stem and the spinal column, and they are responsible for communicating nerve signals from the brain to the muscles and glands. This signaling pathway makes voluntary muscle movement possible. When lower motor neurons can’t effectively communicate with muscles, as in MMA, the ability to move the affected muscles is impacted.

Monomelic Amyotrophy Research

Title: Answer ALS: Individualized Initiative for ALS Discovery (AnswerALS)

Stage: Completed

Principal investigator: Nicholas J. Maragakis, MD

Johns Hopkins University

Baltimore, MD

This study has as its goal the creation of an extensive repository of induced pluripotent stem cells (iPSC), bio-fluid samples (blood and spinal fluid (optional)), and cell lines for ALS gene identification. This will be carefully combined with collected measures of the pattern of the symptoms people with ALS have and how these change over time. In addition, people with other motor neuron diseases and healthy controls will be included as comparisons.

Patients will have 5 study visits; screening, 3, 6, 9, and 12 months. There will be a one-year post-participation follow-up period, during which they will receive an email or phone call interview once every three months. During the first year, samples will be collected, breathing, muscle strength, spasticity, general function, and cognitive behavior will be assessed. Healthy controls will have 2 study visits during which blood samples will be collected and questionnaires given.

Title: Motor Unit Number Estimation (MUNE) in Adults With Spinal Muscular Atrophy (SMA)

Stage: Recruiting

Principal investigator: Bakri Elsheikh, MD

Ohio State University

Columbus, OH

The primary objective of this research protocol is to study and follow the course of motor neuron loss in individuals with spinal muscular atrophy (SMA) using the electrophysiological technique of motor unit number estimation (MUNE). This study is based on the hypothesis that the electrophysiological technique of motor unit number estimation (MUNE) and compound muscle action potential (CMAP) provide sensitive indicators to assess the severity and progression of disease in adults with SMA.

This is a prospective pilot study to determine MUNE and CMAP values in a population of adults with SMA, assess how these electrophysiologic parameters change over time, and explore how well these parameters correlate with other outcome measures in SMA, including functional scales (SMAFRS and SF-36) and muscle strength (by MMT, MVICT, 6-minute walk test, time to climb four stairs and handheld myometry). The study was started in 2006 with four visits. It was initially intended to measure baseline and variability of values at baseline, six months, 10-14 months, and 20-24 months to better characterize the disease and to validate measurements as suitable outcome measures to be used in future therapeutic trials on adults. Individuals who do not take nusinersen would continue on this visit plan.

With the addition of the FDA-approved drug nusinersen for SMA, researchers would like to follow people receiving that treatment more frequently. The visits will fall in relation to their treatment doses. Those patients who are receiving nusinersen will come in at a baseline visit that will be1 to 6 weeks prior to the first treatment. Then they would follow-up one to 2.5 weeks after each treatment dosing that happens quarterly after the initial loading dose. There will be ten visits over three years. The visits will occur at baseline, 2, 6, 10, 14, 18, 22, 26, 30, and 34 months. These additional visits will allow for better uniform monitoring of the response to treatment and resubmission to insurance providers. Additional long-term data will be collected from interested/available patients every 2-3 years up to a max of fifteen years. Being followed by long-term would add 4-6 visits over 12 years. If subjects completed the study course in the past and are now starting nusinersen (SPINRAZA), those individuals can enroll again.

A total of 100 people with SMA will be enrolled in this trial. This will allow for two cohorts of people with SMA; those receiving treatment and those not receiving treatment.

Control participants will only come to a baseline visit and the only tests that will be completed are the EMG Measures (MUNE, CMAP, decomposition EMG) and EIM. There will be no further testing for those participants. This visit will take approximately 30-60 minutes. A total of 40 control participants are being recruited for this study.

Title: Clinical Study of Spinal Muscular Atrophy

Stage: Active

Principal investigator: Darryl C. De Vivo, MD

Columbia University

New York, NY

The investigators propose to prepare for clinical trials where SMA patients are asked to join the research effort. The visits will include questions, physical exam, blood drawing, and sometimes X-rays and a skin biopsy. The investigators will use modern computer methods to process the information to plan a clinical trial. Once the clinical trial begins, the investigators will offer SMA patients participation if they meet the criteria for that trial.

Identifying an effective SMA treatment is very important because there is currently none. Clinical trials are the only way to decide whether a new treatment works in SMA patients or not.

Spinal Muscular Atrophy (SMA) is one of the most devastating neurological diseases of childhood. Affected infants and children suffer from progressive muscle weakness caused by degeneration of lower motor neurons in the spinal cord and brainstem. Clinically, four phenotypes are distinguished within the continuous spectrum of disease severity based on the age of onset and the highest motor milestone ever achieved. SMA is caused by homozygous deletion of the survival motor neuron-1 (SMN1) gene. A related gene, SMN2, produces low levels of full-length SMN protein due to inefficient splicing. There is an inverse correlation between SMN copy number and disease severity, presumably mediated by levels of full-length SMN protein. Therefore, increasing the amount of full-length SMN protein is a promising treatment strategy. Several drugs targeting splicing efficiency have increased SMN protein in preclinical assays and are awaiting clinical testing.

With the future objective to conduct clinical trials in SMA, the proposed project has three specific aims: 1) To establish a web-based database that will serve to enroll the patient population and that will facilitate timely recruitment for future clinical trials; (2) to plan for clinical trials by a) developing reliable outcome measures, and (b) establishing the infrastructure needed to carry out efficient clinical trials, (c) convening meetings of preclinical and clinical researchers involved in SMA drug development to select candidate drugs, and (3) to characterize the patient population from a clinical and molecular point of view.