Rita Di Leo

Cardiovascular autonomic control in myotonic dystrophy type 1: a correlative study with clinical and genetic data

The autonomic nervous system has been evaluated in myotonic dystrophy with contradictory results and its relationship with heart disturbances remains unclear. Twenty-three patients with myotonic dystrophy type 1 were investigated by a battery of six cardiovascular autonomic tests and power spectral analysis of heart rate variability. Although 15 patients (65%) revealed abnormal or borderline results in some tests, only one patient had a definite autonomic damage, as indicated by two or more abnormal tests. As a group, myotonic dystrophy type 1 patients showed a significant reduction of heart rate variability during deep breathing (P < 0.0001). The exclusive involvement of parasympathetic tests suggests that a mild vagal dysfunction occurs in some myotonic dystrophy type 1 patients. The results indicate that such autonomic abnormalities are not: (1) part of a peripheral neuropathy; (2) related to cytosine-thymine-guanine repeat size or breathing pattern. Power spectral analysis showed a reduction of supine low-frequency band, which is, but not exclusively, a marker of sympathetic activity. It was inversely correlated to disease duration (P < 0.04), suggesting a progression as the disease advances. A low-frequency power, recorded after standing, was significantly associated (P < 0.02) with presence of heart involvement. Our findings suggest that a mixed, especially parasympathetic, autonomic dysfunction may occur in myotonic dystrophy type 1, although it is not a major finding. It could play a role in the occurrence of cardiac abnormalities, or increase the risk of sudden cardiovascular events.

Oxidative stress in myotonic dystrophy type 1

Myotonic dystrophy type 1 (DM1) is the most common form of muscular dystrophy affecting adults. The genetic basis of DM1 consists of a mutational expansion of a repetitive trinucleotide sequence (CTG). The number of triplets expansion divides patients in four categories related to the molecular changes (E1, E2, E3, E4). The pathogenic mechanisms of multi-systemic involvement of DM1 are still unclear. DM1 has been suspected to be due to premature aging, that is known to be sustained by increased free radicals levels and/or decreased antioxidants activities in neurodegenerative disorders. Recently, the gain-of-function at RNA level hypothesis has gained great attention, but oxidative stress might act in the disease progression. We have investigated 36 DM1 patients belonging to 22 unrelated families, 10 patients with other myotonic disorders (OMD) and 22 age-matched healthy controls from the clinical, biochemical and molecular point of view. Biochemical analysis detected blood levels of superoxide dismutase (SOD), malonilaldehyde (MDA), vitamin E (Vit E), hydroxyl radicals (OH) and total antioxidant system (TAS). Results revealed that DM1 patients showed significantly higher levels of SOD (+40%; MAL (+57%; RAD 2 (+106%; and TAS (+20%; than normal controls. Our data support the hypothesis of a pathogenic role of oxidative stress in DM1 and therefore confirm the detrimental role played by free radicals in this pathology and suggest the opportunity to undertake clinical trials with antioxidants in this disorder.

Enterococcal meningitis caused by Enterococcus casseliflavus. First case report

BackgroundEnterococcal meningitis is an uncommon disease usually caused by Enterococcus faecalis and Enterococcus faecium and is associated with a high mortality rate. Enterococcus casseliflavus has been implicated in a wide variety of infections in humans, but never in meningitis.Case presentationA 77-year-old Italian female presented for evaluation of fever, stupor, diarrhea and vomiting of 3 days duration. There was no history of head injury nor of previous surgical procedures. She had been suffering from rheumatoid arthritis for 30 years, for which she was being treated with steroids and methotrexate. On admission, she was febrile, alert but not oriented to time and place. Her neck was stiff, and she had a positive Kernigs sign. The patients cerebrospinal fluid was opalescent with a glucose concentration of 14 mg/dl, a protein level of 472 mg/dl, and a white cell count of 200/μL with 95% polymorphonuclear leukocytes and 5% lymphocytes. Gram staining of CSF revealed no organisms, culture yielded E. casseliflavus. The patient was successfully treated with meropenem and ampicillin-sulbactam.ConclusionsE. casseliflavus can be inserted among the etiologic agents of meningitis. Awareness of infection of central nervous system with Enterococcus species that possess an intrinsic vancomycin resistance should be increased.

Transthyretin‐related familial amyloidotic polyneuropathy: description of a cohort of patients with Leu64 mutation and late onset

Transthyretin‐related familial amyloidotic polyneuropathy (TTR‐FAP) usually presents itself as a progressive sensorimotor polyneuropathy with severe autonomic dysfunction and cardiomyopathy. Eighteen patients carrying the Leu64 mutation underwent a series of regular follow‐ups, including: neurological examination, electroneurography, electromyography, electrocardiography and echocardiography, blood analysis, a questionnaire on autonomic symptoms, cardiovascular autonomic tests and a 99mTc‐DPD examination study. A late onset of a slowly progressive disease which reached its terminal stage after about 10  years was observed. The onset was mainly a length‐dependent sensory neuropathy, although a focal onset with carpal tunnel syndrome was detected in three patients. At the onset of the disease, autonomic dysfunction was present in a small number of patients, but, within a few years, this had manifested in all members of the sample group. The only extra‐neurological manifestations were cardiac related. It is reasonable to consider Southern Italy as an endemic focus of TTR‐FAP. An underestimation of disease prevalence could be caused by a late onset of FAP, which can manifest in patients up to their late 70s. Follow‐up of asymptomatic individuals may permit the early detection of symptoms and signs, allowing a detailed record of the natural history of the disease from the beginning and facilitating prompt treatment.

Cardiovascular autonomic control in Becker muscular dystrophy.

Although autonomic symptoms are not prominent in dystrophinopathies, a reduced vagal activity and an enhanced sympathetic tone have been found in Duchenne muscular dystrophy. Twenty patients with Becker muscular dystrophy (BMD) were investigated by a battery of six cardiovascular autonomic tests (beat-to-beat variability during quiet breathing and deep breathing, heart rate responses to Valsalva maneuver and standing, blood pressure responses to standing and sustained handgrip) and power spectral analysis (PSA) of heart rate variability. Although 11 patients revealed abnormal findings at some cardiovascular tests, none of them had a definite autonomic damage, as indicated by two or more abnormal tests. The mean results of the single tests did not differ from normal controls, except for the beat-to-beat variability during quiet breathing, which was significantly higher in BMD (p<0.05). Such finding was confirmed by a significantly higher total variance (p<0.05), indicating an increased parasympathetic activity. Spectral components were not significantly different from normal controls. PSA values were not influenced by age, functional ability score or presence of heart abnormalities. Our data suggest that autonomic involvement does not represent a major finding in BMD.

Recurrent syncope as persistently isolated feature of transthyretin amyloidotic polyneuropathy

In transthyretin familial amyloid polyneuropathy (TTR-FAP), single clinical features rarely remain isolated and are usually accompanied by other symptoms. We describe a patient with TTR-FAP, who had recurrent episodes of syncope for 4 years as an overt and isolated symptom. Later, he experienced paresthesia in the hands, and impotence. Molecular analysis of the TTR gene revealed a Thr49Ala mutation. The unusual clinical presentation presents a diagnostic challenge.

Charcot–Marie–Tooth 2F: phenotypic presentation of the Arg136Leu HSP27 mutation in a multigenerational family

Abstract Mutations in the small heat-shock protein HSP27 gene are associated with distal hereditary motor neuropathy and with the axonal form of Charcot–Marie–Tooth disease type 2. We present the clinical and electrophysiological data on a multigenerational family with the p.Arg136Leu HSP27 mutation. Atypical features such as deafness and pyramidal signs were present in our cases adding new data to the large spectrum of HSP27-related phenotype.

Peripheral neuropathy as the presenting feature of multiple system atrophy

The authors report a case of multiple system atrophy (MSA) with an onset as a peripheral nerve involvement. Their patient, a 55-year-old man, had a 3-year history of distal weakness and atrophy in upper limbs with dysesthesia in the feet. Other identifiable causes of peripheral neuropathy were ruled out. The authors postulate that peripheral nervous system impairment can anticipate the typical appearance of MSA, and they suggest that, in peripheral neuropathies with autonomic system dysfunction, after excluding main causes of autonomic neuropathy, MSA may need to be suspected.

Autonomic involvement in subacute and chronic immune-mediated neuropathies.

Autonomic function can be impaired in many disorders in which sympathetic, parasympathetic, and enteric arms of the autonomic nervous system are affected. Signs and symptoms of autonomic involvement are related to impairment of cardiovascular, gastrointestinal, urogenital, thermoregulatory, sudomotor, and pupillomotor autonomic functions. Availability of noninvasive, sensitive, and reproducible tests can help to recognize these disorders and to better understand specific mechanisms of some, potentially treatable, immune-mediated autonomic neuropathies. This paper describes autonomic involvement in immune-mediated neuropathies with a subacute or chronic course.

Autonomic regulation in muscular dystrophy

Autonomic Nervous System (ANS) function has been assessed in several muscular dystrophies. In the last two decades it has been recognized a significant relationship between ANS and cardiac mortality (Politano et al., 2008). Cardiovascular ANS is frequently studied by using cardiovascular autonomic reflex tests and spectral analysis of heart rate in time and frequency domain (Ewing and Clarke, 1982; van Ravenswaaij-Arts et al., 1993). Heart rate variability (HRV) analysis, which involves measurement and analysis of heart rate variation, provides a quantitative marker of autonomic activity and has proved to be able to detect and measure modification in sympathetic or vagal activity. Moreover, it can be used to estimate the susceptibility for heart arrhythmias (Heart rate variability, 1996a,b).