Electroretinographic and visual evoked potential abnormalities in myotonic dystrophy

Pattern visual evoked potentials (VEPs) and electroretinograms (ERGs) were recorded in 20 patients with myotonic dystrophy. Thirteen out of 20 cases presented both VEP and ERG abnormalities, 3 only ERG alterations, 2 only abnormal VEPs. A significant inverse correlation between P100 latencies and b1 wave amplitude was observed, while N1-P100 and b1 wave amplitude exhibited a parallel change. These data suggest that retinal abnormalities may have a role in inducing subclinical visual pathway alterations in myotonic dystrophy.     

Cerebral abnormalities in congenital myotonic dystrophy

The brain structure of 14 infants born with congenital myotonic dystrophy at 2 hospitals was evaluated by cranial ultrasonography, and the findings were correlated with clinical and neuropathologic data. Ventricular dilation was diagnosed in 11 infants (78%). Seven infants died during the neonatal period; all had ventricular dilation which remained essentially static. In the ultrasound scans of the 5 infants with ventricular dilation. Of the 7 survivors, 4 had ventricular dilation born at 1 hospital, 4 had widening of the interhemispheric fissure. Macrocephaly, a previously unrecognized finding in congenital myotonic dystrophy, was present in 10 infants (71%), 8 of whom presented with ventricular dilation. None had clinical evidence of increased intracranial pressure. There was no ventricular obstruction in the 4 brains examined pathologically. Histologic examination revealed minor expression of neuronal migrational disturbances in each patient. Macrocephaly together with the ultrasonographic and neuropathologic findings in our patients suggest that these abnormalities may originate in an external hydrocephalus.     

Immunoglobulin abnormalities in patients with myotonic dystrophy

In order to further investigate immunoglobulin (Ig) abnormalities in patients with myotonic dystrophy (MyD), we examined 65 patients with MyD for their serum concentration of IgG in relation to their immunological functions as well as other clinical and laboratory findings. Turnover of IgG was also examined. We found significant and selective reduction of serum IgG in patients with MyD. The serum concentration of IgG in patients with MyD had a significant negative correlation with duration of illness, which suggested that serum IgG levels in MyD decreased constantly throughout the disease course. Peripheral blood lymphocyte subpopulations, including functional T cell subsets, in vitro lymphocyte proliferation, and in vitro IgG production were normal. The plasma cell population in bone marrow was also normal. The IgG turnover study using 125I-labelled IgG as a tracer revealed an increased extravascular IgG pool, and an increased capillary permeability of intravascular IgG into the extravascular compartment, in patients with MyD. These observations suggested that the Ig abnormalities in patients with MyD were not due to a broader immunological derangements as previously postulated by other authors. The abnormal distribution of IgG is a possible factor leading to reduced serum concentration of IgG in patients with MyD.     

Erythrocyte membrane abnormalities in human myotonic dystrophy

Membrane-bound enzyme activities and cardiac glycoside binding were determined in red blood cell membrane preparations from patients with myotonic dystrophy and in age matched controls. Na⁺-K⁺-activated ATPase activity was signficantly increased in myotonic patients. [³H]Ouabain binding to erythrocyte membranes was also significantly increased in myotonic dystrophy patients. The Mg²⁺-ATPase (ouabain-insensitive) was, however, unchanged. The K⁺-stimulated paranitrophenyl phosphatase (KPNPPase) activity was markedly enhanced in myotonic patients as compared to controls. The kinetic analysis showed a marked change in V_max of Na⁺-K⁺ ATPase with respect to the activation by Na⁺, K⁺ and ATP. However, the K_m values were the same in control as well as in myotonic groups. The increased erythrocyte membrane Na⁺-K⁺-ATPase activity, KPNPPase and [³H]ouabain binding in myotonic patients supports the hypothesis that generalized membrane abnormality may be involved in pathogenesis of the human myotonic dystrophy.     

Cerebral and muscle MRI abnormalities in myotonic dystrophy

Pathophysiological mechanisms underlying the clinically devastating CNS features of myotonic dystrophy (DM) remain more enigmatic and controversial than do the muscle abnormalities of this common form of muscular dystrophy. To better define CNS and cranial muscle changes in DM, we used quantitative volumetric and diffusion tensor MRI methods to measure cerebral and masticatory muscle differences between controls (n=5) and adults with either congenital (n=5) or adult onset (n=5) myotonic dystrophy type 1 and myotonic dystrophy type 2 (n=5). Muscle volumes were diminished in DM1 and strongly correlated with reduced white matter integrity and gray matter volume. Moreover, correlation of reduced fractional anisotropy (white matter integrity) and gray matter volume in both DM1 and DM2 suggests that these abnormalities may share a common underlying pathophysiological mechanism. Further quantitative temporal and spatial characterization of these features will help delineate developmental and progressive neurological components of DM, and help determine the causative molecular and cellular mechanisms.     

Somatosensory evoked potential recovery in myotonic dystrophy.

OBJECTIVE: To evaluate recovery functions of the sensory cortex using somatosensory evoked potentials (SEPs) elicited by paired stimuli of the median nerve in patients with myotonic dystrophy (MD). SUBJECTS/METHODS: Twelve MD patients were enrolled in the present investigation. Five patients with facioscapulohumeral muscular dystrophy (FSH) and 12 healthy volunteers were studied as control groups. SEP was recorded from the hand sensory area contralateral to the median nerve stimulated at the wrist. Single pulse or paired-pulse stimuli at various interstimulus intervals (ISIs) (10, 20, 40, 60, 80, 100, 150, 200 and 300 ms) were given. Recovery functions of N9, N20onset-N20peak, N20-P25 and P25-N33 components were studied. RESULTS: Conventional SEPs to a single stimulus were normal in the latency and amplitude in all the patients. Recovery functions of both N9 and N20o-N20p components were normal in the patients. In contrast, in MD patients, disinhibited or hyperexcitable recovery pattern was observed in recovery curves of the N20-P25 or P25-N33 components, whereas those were normal in FSH patients. CONCLUSIONS: Disinhibited cortical excitability (or hyperexcitability) is present in the sensory cortex in patients with myotonic dystrophy. This may reflect cortical pathology or functional alteration of the sensory cortex in MD.     

Laboratory abnormalities in ambulatory patients with myotonic dystrophy type 1

BACKGROUND: Myotonic dystrophy type 1 (DM1) is the most prevalent form of adult muscular dystrophy worldwide. Although well known for the classic manifestations of myotonia, weakness, and early cataracts, it has broad effects on multiple organ systems. OBJECTIVE: To analyze and compile the laboratory abnormalities of 126 adult patients with DM1. DESIGN: Laboratory data obtained before treatment were compiled and include values for 45 different laboratory tests and 2860 total studies. SETTING: University hospital. PATIENTS: One hundred twenty-six medically healthy, mild to moderately affected, ambulatory patients with DM1 and good venous access enrolled in one of 12 major DM1 clinical trials at a university hospital from 1975 to 2005. RESULTS: Of the 2860 laboratory studies, results for 470 (16.4%) were outside their reference ranges. Of the 45 types of laboratory tests studied, 41 demonstrated abnormal findings. The relative frequency of an abnormally elevated laboratory value was greater than 50% in several tests, including levels of hemoglobin A(1c), follicle-stimulating hormone, luteinizing hormone in men, and gamma-glutamyltransferase and creatine kinase in women. In addition, levels of lactate dehydrogenase in men and hemoglobin in women were abnormally high or low in more than 50% of the test results evaluated. CONCLUSION: There is a high frequency of abnormal laboratory values in DM1 that may form a basis for early screening and monitoring and provide insight into the spectrum of tissues involved in this disease.     

Evoked potential study in facio-scapulo humeral muscular dystrophy

Nerve conduction velocities (NCVs), somatosensory (SEPs) and auditory evoked potentials (BAEPs) were recorded in 9 patients with facio-scapulo-humeral dystrophy (FSHD) and in 20 age-matched controls. In FSHD patients a significant increase of the nerve distal sensory latencies and of the absolute SEP latencies revealed a subclinical involvement of the afferent sensory pathways, as well as the abnormal slowing of the later components of the BAEPs, pointed to a central auditory dysfunction. Moreover all patients underwent brain MRI that showed the presence of white matter hyperintense lesions in 4 of them (44%). No correlations were found between individual or total number of SEP and BAEP abnormal electrophysiological parameters and severity of WMHL, age, age at onset, duration of the disease or muscular impairment. These findings make the interpretation and pathophysiology of the nervous damage in FSHD rather uncertain. More studies are required to better define the aspects of neurogenic involvement in this type of muscular dystrophy.     

Evoked potential abnormalities in the various inherited ataxias

Visual (VEP), brainstem auditory (BAEP), and somatosensory (SEP) evoked potential tests were performed in 45 patients representing ten types of inherited disorders in which ataxia was the most prominent symptom. Comparable VEP abnormalities were present among all types of patients. Normal BAEP tests were recorded in most patients except those with olivopontocerebellar atrophy. SEP results were often more severely abnormal in patients with Friedreich's ataxia. The observations emphasize the similarity in expression of different metabolic-degenerative disorders. When these tests are used clinically, certain features of evoked potentials (especially left-right symmetry) are typical of the inherited ataxias as a group. Few distinguishing features differentiate the individual disorders.     

Ocular motor myotonic phenomenon in myotonic dystrophy

OBJECTIVE: To detect disconjugate ocular motor abnormalities and a possible extraocular muscle myotonic phenomenon in patients with myotonic dystrophy (MyD). METHODS: The magnetic scleral search coil technique was used to record monocularly the small (25 degrees ) and large (50 degrees ) saccades, which were paced to two interstimulus intervals (ISIs), one short (1 s), the other long (5 s). The case study comprised 20 patients with MyD, 10 patients with multiple sclerosis (MS), and 10 controls. The amplitude, duration, peak velocity, and skewness of the velocity profile (ratio between the acceleration and the deceleration periods) of each saccade were measured. The disconjugate parameters (difference between the two eyes of the same measure), and the myotonic parameter (the maximal (as absolute value) short-long ISI difference between the same measures) were considered. RESULTS: The disconjugate parameters were the same in all three groups. The mean values of myotonic parameters found in patients with MyD for duration (for both small and large target displacements) and skewness (for small target displacements only) differed from those found for both the MS and the control groups. Additionally, the occurrence of individual patients presenting with abnormal duration and skewness parameters was higher in the MyD than in the MS group. In patients with MyD, the saccade duration was longer for long than for short ISI; the effect derived from a prolongation of the acceleration period, which manifested as an increase in skewness. CONCLUSION: The results can be explained by a combination of the myotonic and the warm up phenomena. A delay in the relaxation (myotonia) of the extraocular muscle may be more evident after a long fixation period (long ISI) and it may improve by increasing saccade pacing (short ISI-warm up). This phenomenon is slight, and is unlikely to affect saccade performance significantly, but it may provide some insight into the nature of the disorder affecting extraocular and skeletal muscles in myotonic dystrophy.     

Gastroparesis in myotonic dystrophy 1

Clinicians should consider impaired gastric emptying when evaluating patients with myotonic dystrophy type 1 and severe symptoms of upper gut dysmotility. Gastric emptying time measurement by radionuclide study, although informative, is rarely done in clinical practice.     

Creatine monohydrate in myotonic dystrophy

We assessed safety and efficacy of creatine monohydrate (Cr) in myotonic dystrophy (DM1) in a double-blind, cross-over trial. Thirty-four patients with defined DM1 were randomized to receive Cr and placebo for eight weeks (10.6 g day 1–10, 5.3 g day 11–56) in one of 2 treatment sequences. There was no significant improvement using manual and quantitative muscle strength, daily-life activities, and patients' own global assessment comparing verum with placebo administration. Cr supplementation was well tolerated without clinically relevant side effects, but did not result in significant improvement of muscle strength or daily-life activities. Received: 1 May 2002, Received in revised form: 5 July 2002, Accepted: 12 July 2002 Correspondence to Dr. M. C. Walter     

Hypothalamic-pituitary function in myotonic dystrophy

Summary Function of the hypothalamic-pituitary axis was investigated in seven patients with myotonic dystrophy (MD).HGH and ACTH secretion were normal.TSH response to TRH was impaired in about half the cases, without concomitant thyroid dysfunction. LH and FSH levels were often elevated, with inconsistant response to LH-RH stimulation. Gonadotrophin disturbances in MD have previously been attributed to a primary gonadal lesion, characteristically seen in this disease. High prolactin levels in six of our seven patients however suggest that gonadal failure may also be due to hyperprolactinemia through the direct anti-gonadal effect of prolactin and its interference with hypothalamic-pituitary regulation of gonadotrophin secretion.

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Zusammenfassung Bei sieben Patienten mit Myotonia Dystrophica (MD) wurde die hypothalamische-hypophysäre Funktion untersucht. Die Sekretion von HGH und ACTH waren normal. Die TSH-Produktion nach Stimulation mit TRH war in ungefähr der Hälfte der Fälle gestört, ohne begleitende Schilddrüsendysfunktion. LH- und FSH-Werte waren öfters erhöht mit wechselnder Reaktion auf LHRH-Stimulation.Die bisher beschriebenen Gonadotrophinstörungen bei der MD wurden bisher immer dem primären Gonadenleiden zugeschrieben. Erhöhte Prolactin-Werte in sechs unserer sieben Patienten sprechen zugunsten der Möglichkeit, daß die Gonadeninsuffizienz auch eine Folge der Hyperprolactinämie sein könnte sowohl durch eine direkte antigonadale Wirkung, wie durch Interferenz mit der hypothalamisch-pituitären Regulation der Gonadotrophin-Sektretion.

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Abbreviations ACTH adrenocorticotrophic hormone - FSH follicle stimulating hormone - HGH human growth hormone - LH luteinizing hormone - LH-RH luteinizing hormone-releasing hormone - PRL prolactin - TRH thyrotrophic releasing hormone - TSH thyroid stimulating hormone     

Lymphocyte capping in myotonic dystrophy

Lymphocyte capping with antihuman immunoglobulin was studied in 16 cases of myotonic dystrophy, including two cases with the congenital form. Percentage capping after 1 hour incubation was reduced and the time course of the capping sequence was apparently delayed. The significance of these findings remains to be determined.