In a small study of 24 patients with genetically confirmed mitochondrial mutations, researchers were able to discriminate between healthy controls and patients and between the two types of mitochondrial mutations assessed (m.3243A>G and m.8344A>G) based upon gait. Both patient groups were selected because of the known associations between those mitochondrial genotypes and gait disturbances. The questions were whether the pattern of gait disturbance could distinguish between the two groups and whether the gait disturbances could be detected early in the disease process before other symptoms fully emerged. That is, could the way patients walked be diagnostic of incipient mitochondrial disease?
About the Mitochondrial Mutations and Patients Tested
The first mutation m.3243A>G (n=18) is associated a disease called MELAS, which stands for mitochondrial encephalopathy, lactic acidosis, stroke like episodes. It is believed to represent one of the more common classes of mitochondrial mutation. The MELAS mutations are associated with a constellation of additional clinical symptoms, including Chronic Progressive External Ophthalmoplegia (CPEO; weakness in the eye muscles causing eyelid drooping), Maternally Inherited Deafness and Diabetes (MIDD), migraine, bowel problems and short stature.
The second mutation, m.8344A>G is associated with a rare mitochondrial disease called MERRF or myoclonic epilepsy with ragged-red fibers. The cardinal symptoms of MERRF include: muscle twitches (myoclonus), weakness (myopathy), and progressive stiffness (spasticity). However, like with MELAS and other mitochondrial diseases, the clinical presentation of symptoms is diverse with the myoclonic seizures developing in only 1 in 5 MERRF individuals. The remainder of patients present with a variety of symptoms including, generalized seizures, ataxia, cognitive decline, hearing loss, eyelid drooping, multiple lipomas (fatty growths or lumps between the skin and muscle), cardiomyopathy, neuropathy, exercise intolerance, increased creatine kinase levels. Individuals with the MERRF mutation may also have increased muscle wasting, respiratory impairment, diabetes, muscle pain, tremor and migraine.
Testing Gait: Walking, Balance, Energy and Strength Disturbances
For this study, researchers looked at five variables associated with gait disturbances:
- Pace (step velocity and step length)
- Rhythm (step time)
- Variability (step length and step time variability)
- Asymmetry (step time asymmetry)
- Postural stability (step width, step width variability and step length asymmetry)
The gait testing involved walking on a sensor embedded mat which then calculated the above parameters. Additionally, the researchers assessed:
- Mutation load with urinary epithelial testing
- Energy expenditure (a body-worn multi-sensor)
- Exercise capacity (peak oxygen consumption, heart rate response)
- Muscle strength (hip flexor ad extensor strength)
- MRI when available
Compared to the healthy controls, individuals with mitochondrial disease demonstrated significantly reduced gait speed; they walked much more slowly. They also took smaller steps and had increase step time, width and length variability. Individuals with the MERRF mutations were noticeably worse and more globally impaired than those with the MELAS mutations and individuals bearing higher mutation loads and a longer disease trajectory performed most poorly. Universally reduced energy expenditure, exercise capacity and hip flexion and extension strength was observed across both patient groups compared to controls.
One of the more interesting and perhaps unanticipated findings was the association between aspects of gait and cerebellar atrophy. As might be expected, disturbances is balance and symmetry were correlated with cerebellar atrophy. What was interesting is that subtle changes in step width and length variability were observable in individuals with low mutation loads and who otherwise presented with fewer clinical symptoms, suggesting step variability may among the first signs of cerebellar involvement, before full blown ataxia is observed. If this bears out in additional research, walking may become an easy mechanism to test for mitochondrial dysfunction.
Connecting a Few Dots: Medication and Vaccine Induced Mitochondrial Dysfunction
Across many of the patient groups we work with at Hormones Matter, ataxia is a common symptom post medication and vaccine reaction and among individuals with thyroid disease (here and here). Often the ataxia presents with an array of other symptoms associated with mitochondrial disease, seizures, migraines, tremors, GI dysmotility, muscle weakness, neuropathy, to name a few. Since genotyping has not been conducted with these patients, it is not clear whether the medication or vaccine simply unmasked and expedited a latent mitochondrial mutation, triggered a functional mitochondrial deficit with symptoms corresponding with those manifested by more traditional genetic mutations, or some combination of both. Whatever the cause, however, it is becoming increasingly clear that many of the adverse reactions share phenotypes and follow trajectories similar to those associated with mitochondrial disease. Cerebellar involvement, being key among them. Based upon the research cited above, gait disturbances ought to be considered more closely and viewed as a marker of mitochondrial disease or dysfunction, particularly when the constellation of other mitochondrial associated symptoms presents concurrently.
We Need Your Help
More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.
This article was posted originally October 13, 2014.