RESUMEN
Background: Myotonic dystrophy type 1 (DM1) is a rare multisystemic genetic disorder with motor hallmarks of myotonia, muscle weakness and wasting. DM1 patients have an increased risk of falling of multifactorial origin, and proprioceptive and vestibular deficits can contribute to this risk. Abnormalities of muscle spindles in DM1 have been known for years. This observational cross-sectional study was based on the hypothesis of impaired cervical proprioception caused by alterations in the neck spindles. Methods: Head position sense was measured in 16 DM1 patients and 16 age- and gender-matched controls. A head-to-target repositioning test was requested from blindfolded participants. Their head was passively rotated approximately 30° leftward or rightward and flexed or extended approximately 25°. Participants had to replicate the imposed positions. An optoelectronic system was adopted to measure the angular differences between the reproduced and the imposed positions (joint position error, JPE, °) concerning the intended (sagittal, horizontal) and unintended (including the frontal) planar projections. In DM1 patients, JPEs were correlated with clinical and balance measures. Static balance in DM1 patients was assessed through dynamic posturography. Results: The accuracy and precision of head repositioning in the intended sagittal and horizontal error components did not differ between DM1 and controls. On the contrary, DM1 patients showed unintended side-bending to the left and the right: the mean [95%CI] of frontal JPE was -1.29° [-1.99°, -0.60°] for left rotation and 0.98° [0.28°, 1.67°] for right rotation. The frontal JPE of controls did not differ significantly from 0° (left rotation: 0.17° [-0.53°, 0.87°]; right rotation: -0.22° [-0.91°, 0.48°]). Frontal JPE differed between left and right rotation trials (p < 0.001) only in DM1 patients. No correlation was found between JPEs and measures from dynamic posturography and clinical scales. Conclusions: Lateral head bending associated with head rotation may reflect a latent impairment of neck proprioception in DM1 patients.
RESUMEN
Lafora disease is a rare genetic disorder characterized by a disruption in glycogen metabolism. It manifests as progressive myoclonus epilepsy and cognitive decline during adolescence. Pathognomonic is the presence of abnormal glycogen aggregates that, over time, produce large inclusions (Lafora bodies) in various tissues. This study aims to describe the clinical and histopathological aspects of a novel Lafora disease patient, and to provide an update on the therapeutical advancements for this disorder. A 20-year-old Libyan boy presented with generalized tonic-clonic seizures, sporadic muscular jerks, eyelid spasms, and mental impairment. Electroencephalography showed multiple discharges across both brain hemispheres. Brain magnetic resonance imaging was unremarkable. Muscle biopsy showed increased lipid content and a very mild increase of intermyofibrillar glycogen, without the polyglucosan accumulation typically observed in Lafora bodies. Despite undergoing three lines of antiepileptic treatment, the patient's condition showed minimal to no improvement. We identified the homozygous variant c.137G>A, p.(Cys46Tyr), in the EPM2B/NHLRC1 gene, confirming the diagnosis of Lafora disease. To our knowledge, the presence of lipid aggregates without Lafora bodies is atypical. Lafora disease should be considered during the differential diagnosis of progressive, myoclonic, and refractory epilepsies in both children and young adults, especially when accompanied by cognitive decline. Although there are no effective therapies yet, the development of promising new strategies prompts the need for an early and accurate diagnosis.
RESUMEN
Falls are frequent in Myotonic Dystrophy type 1 (DM1), but the pathophysiology of the balance impairment needs further exploration in this disease. The current work aims to provide a richer understanding of DM1 imbalance. Standing balance in 16 patients and 40 controls was tested in two posturographic tests (EquiTest™). In the Sensory Organization Test (SOT), standstill balance was challenged by combining visual (eyes open vs. closed) and environmental conditions (fixed vs. sway-tuned platform and/or visual surround). In the "react" test, reflexes induced by sudden shifts in the support base were studied. Oscillations of the body centre of mass (COM) were measured. In the SOT, COM sway was larger in patients than controls in any condition, including firm support with eyes open (quiet standing). On sway-tuned support, COM oscillations when standing with closed eyes were larger in patients than controls even after taking into account the oscillations with eyes open. In the "react" paradigm, balance reflexes were delayed in patients. Results in both experimental paradigms (i.e., SOT and react test) are consistent with leg muscle weakness. This, however, is not a sufficient explanation. The SOT test highlighted that patients rely on vision more than controls to maintain static balance. Consistently enough, evidence is provided that an impairment of proprioceptive and vestibular systems contributes to falls in DM1. Rehabilitation programs targeted at reweighting sensory systems may be designed to improve safe mobility in DM1.