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S Iannaccone

Publications and source records attributed to S Iannaccone.

At least 19 recordsLinked to original sources
PubMed2005

Challenges and opportunities in clinical trials for spinal muscular atrophy.

Spinal muscular atrophy (SMA) is the most common fatal neuromuscular disease of infancy. SMA type I is the most severe and mortality is usually due to respiratory failure. In type II the disability is of later onset and less severe, and prognosis has improved primarily due to supportive care. Type III is the mildest form with onset usually of weakness in adolescence or young adulthood. SMA is an autosomal recessive disorder with deletions or mutations of the gene at the 5 q11 locus. There is no specific prevention or treatment, but current progress toward potential therapies has been substantial and several candidates including histone deacetylase (HDAC) inhibitors are under consideration for further evaluation. The authors sought to address the challenges and opportunities for testing new therapies for SMA.

Child↗
PubMed2005

Dominant LMNA mutations can cause combined muscular dystrophy and peripheral neuropathy.

The coexistence of neurogenic and myogenic features in scapuloperoneal syndrome is rarely ascribed to a single gene. Defects in the nuclear envelope protein lamin A/C, encoded by the LMNA gene, have been shown to be associated with a variety of disorders affecting mainly the muscular and adipose tissues and, more recently, with autosomal recessive Charcot-Marie-Tooth type 2 neuropathy. This report is about a patient presenting features of myopathy and neuropathy due to a dominant LMNA mutation, suggesting that the peripheral nerve might be affected in primary LMNA myopathy. Our observations further support the marked intrafamilial and interfamilial phenotypic heterogeneity associated with lamin A/C defects.

Adolescent↗
PubMed2001

A placebo-controlled trial of gabapentin in spinal muscular atrophy.

OBJECTIVE: To evaluate the efficacy of gabapentin in increasing muscle strength of patients with spinal muscular atrophy (SMA). BACKGROUND: Preclinical data in experimental models of motor neuron disease suggest a neuroprotective effect of gabapentin. METHODS: Gabapentin (1200 mg), or placebo, was administered three times daily in a randomized, double-blind trial for 12 months. The primary outcome measure was the average percent change from baseline, based on the measurement of strength in four muscles (elbow flexion and hand grip bilaterally) for each patient. Drug efficacy was examined by comparing the percent change in strength for patients on drug vs. placebo. Secondary efficacy variables included: forced vital capacity (FVC), SMA functional rating scale (SMAFRS), and mini-Sickness Impact Profile (SIP). RESULTS: Eighty-four patients, with type II or III SMA, were enrolled at eight sites across the United States. There were no differences in baseline features. There was no difference between the placebo and drug groups in any outcome measure. CONCLUSIONS: This study demonstrates the feasibility of this trial design and provides data for the design of future clinical trials in SMA.

Acetates↗
PubMed2001

[Death in an unusual body position].

Death in head-down position is rare and uncommon. The mechanism of death in such cases is rather complicated. The authors present a case of unknown man who was found dead in a wood, hanging in head-down position fixed at the branchfork of a tree by his right foot. The authors analyse the possible mechanisms of death in so-called postural asphyxia.

Accidents↗
PubMed1999

The exercise test in Andersen syndrome.

BACKGROUND: Andersen syndrome is a rare form of periodic paralysis (PP) associated with dysmorphic features and potentially fatal cardiac dysrhythmias. To date, no electrodiagnostic abnormalities have been reported that can be used to confirm the presence of PP in this condition. OBJECTIVES: To determine if the exercise test could be used to confirm the diagnosis of PP in Andersen syndrome. To evaluate the exercise test as a means to assess neuromuscular status during treatment. METHODS: We performed the exercise test on 2 patients with Andersen syndrome. In 1 patient, we used a modified version of the test to document responsiveness to treatment with tocainide. RESULTS: Studies in both patients demonstrated a progressive decline in the compound muscle action potential amplitude after exercise that was characteristic of the phenomenon seen in other forms of PP. In 1 patient, improvement in interattack strength and a reduction in the number of attacks of weakness correlated with improvement in the test results. CONCLUSIONS: Our cases demonstrate that the exercise test can confirm the diagnosis of PP in Andersen syndrome. A modified version of exercise testing may also be considered as an objective method for documenting treatment responses in PP.

Abnormalities, Multiple↗
PubMed1999

Clinical and genetic heterogeneity in autosomal recessive nemaline myopathy.

Autosomal recessive nemaline (rod) myopathy is clinically and genetically heterogeneous. A clinically distinct, typical form, with onset in infancy and a non-progressive or slowly progressive course, has been assigned to a region on chromosome 2q22 harbouring the nebulin gene Mutations have now been found in this gene, confirming its causative role. The gene for slow tropomyosin TPM3 on chromosome 1q21, previously found to cause a dominantly inherited form, has recently been found to be homozygously mutated in one severe consanguineous case. Here we wished to determine the degree of genetic homogeneity or heterogeneity of autosomal recessive nemaline myopathy by linkage analysis of 45 families from 10 countries. Forty-one of the families showed linkage results compatible with linkage to markers in the nebulin region, the highest combined lod scores at zero recombination being 14.13 for the marker D2S2236. We found no indication of genetic heterogeneity for the typical form of nemaline myopathy. In four families with more severe forms of nemaline myopathy, however, linkage to both the nebulin and the TPM3 locus was excluded. Our results indicate that at least three genetic loci exist for autosomal recessive nemaline myopathy. Studies of additional families are needed to localise the as yet unknown causative genes, and to fully elucidate genotype-phenotype correlations.

Child↗
PubMed1999

Central nervous system superficial siderosis, headache, and epilepsy.

Almost 95 cases of superficial siderosis of the central nervous system have been reported in the literature. These patients showed a clinical syndrome characterized by ataxia, deafness, pyramidal system involvement, and mental deterioration with xanthochromic cerebrospinal fluid and neuroradiological findings of hemosiderin deposits. About 30% of the patients had headache as an accompanying symptom. In the present case report, we describe a 33-year-old man with the typical clinical features of superficial siderosis, who complained, since aged 8, of a severe recurrent frontal headache often associated with loss of consciousness occurring after at least 2 hours of pain. The MRI and CSF findings were consistent with subarachnoid bleeding. In our patient, headache due to meningeal irritation by subarachnoid blood induced seizures as a probable reflex of extreme pain. Carbamazepine and nimodipine prophylaxis dramatically reduced the frequency of headaches and seizures.

Adult↗
PubMed1998

Genital plus audiovisual sexual stimulation following intracavernous vasoactive injection versus re-dosing for erectile dysfunction--results of a prospective study.

PURPOSE: We assessed whether re-dosing of a vasoactive agent or the combination of a vasoactive injection and genital plus audiovisual sexual stimulation caused the greatest erectile effect to determine which of the 2 procedures would be better for dynamic penile color Doppler sonography in patients with erectile dysfunction. MATERIALS AND METHODS: A total of 20 consecutive patients with erectile dysfunction underwent 2 sessions under real-time RigiScan* recording of penile erection. Session 1 consisted of adaptation in 10 minutes, intracavernous injection of 10 micrograms. alprostadil in 10 minutes and re-dosing of 10 micrograms. alprostadil in 10 minutes. Session 2 consisted of adaptation in 10 minutes, injection of 10 micrograms. alprostadil in 10 minutes and genital plus audiovisual sexual stimulation in 10 minutes. The total duration of each session was 30 minutes. The order of the 2 sessions was randomly assigned with a week interval between each session. RESULTS: Re-dosing and genital plus audiovisual sexual stimulation caused a significant increase in erectile response compared to the result seen after the first injection (re-dosing p < 0.05, injection plus stimulation p < 0.01). However, erectile response after the genital stimulation session was significantly greater than that after re-dosing (p < 0.01). An erection comparable to the greatest spontaneous erection reported by the patient was much more frequently achieved after genital stimulation than after the re-dosing session (p < 0.01). CONCLUSIONS: The combination of injection and stimulation caused a significantly greater erectile response than re-dosing. We suggest that the former should always be used during color Doppler sonography to optimize the accuracy of the test. Re-dosing is suggested when an incomplete erectile response occurs after the injection plus stimulation phase.

Adult↗
PubMed1998

Amyloid neuropathy simulating lower motor neuron disease.

We report a 57-year-old man with progressive symmetric weakness and fasciculation affecting the legs. Electromyography revealed fibrillations and neurogenic motor unit potentials in the leg muscles. Biopsy of a motor branch of the obturator nerve revealed axonal degeneration, loss of myelinated nerve fibers, and amyloidosis with deposits of lambda light chains. At 6-month follow-up, the patient manifested sensory and autonomic symptoms, and lambda light chains were first detected in the serum. In this case, diagnosis of amyloidosis remained elusive until motor nerve biopsy.

Amyloid Neuropathies↗
PubMed1998

Muscle fibre type and obstructive sleep apnea.

Muscular pharyngeal structural changes, as fibre type disproportion, have been described in patients affected by Obstructive Sleep Apnea (OSA) and in an animal experimental OSA model. The unsolved question is whether these muscular abnormalities are either secondary to a compensatory increased activity or due to a constitutionally determined reduction of slow-alpha motor neurons. In the present study Medium Pharyngeal Constrictor Muscles (MPCM) of OSA (n = 13) and non-OSA (n = 9) patients have been morphologically evaluated. In addition a needle biopsy of Vastus Lateralis Muscle (VLM) was performed in 5 randomly selected patients of each group. Our results confirmed a specific fibre type disproportion of MPCM of OSA patients compared to non-OSA ones with a type II predominance and aspecific myopathic changes such as fibrosis and central nuclei. No difference was found in the VLM of the two groups. This finding could be explained by a secondary adaptive transformation consequent to nocturnal upper airway resistance in OSA. In fact, it has been demonstrated in human muscle that heavy-resistance training may produce preferential type II fibre hypertrophy in stimulated muscle.

Adaptation, Physiological↗
PubMed1997

Motor nerve biopsy studies in motor neuropathy and motor neuron disease.

The clinical presentation of motor neuropathy often resembles that of motor neuron disease, sometimes leading to an erroneous diagnosis. Moreover, the underlying pathological process in motor neuropathy has been rarely investigated and there are no systematic studies of the affected motor nerves. We describe a new motor nerve biopsy procedure, performed in 15 patients: 6 with motor neuropathy and 9 with motor neuron disease. The motor branch from the anterior division of the obturator nerve to the gracilis muscle in the thigh was biopsied. In both groups of patients the motor nerves exhibited depletion of myelinated nerve fibers. In motor neuropathy there was a significantly higher density of regenerative clusters of small myelinated fibers in comparison to motor nerves from patients with motor neuron disease. In addition, in 3 patients with motor neuropathy there was evidence for demyelination with thinly myelinated axons and small onion bulb formations. These pathological studies of motor nerve biopsies can help to differentiate motor neuropathy from motor neuron disease.

Adult↗
PubMed1997

Andersen's syndrome: a distinct periodic paralysis.

A previous study of 4 patients defined Andersen's syndrome (AS) as a triad of potassium-sensitive periodic paralysis, ventricular dysrhythmias, and dysmorphic features. AS appears to be distinct in terms of its genetic defect from the alpha-subunit of skeletal muscle sodium channel and the cardiac potassium channel responsible for most long QT syndromes (LQT1). We studied 11 additional patients with AS from 5 kindreds. Spontaneous attacks of paralysis were associated with hypokalemia, normokalemia, or hyperkalemia. All 11 patients had similar dysmorphic features. The QT interval was prolonged in all patients although only 4 were symptomatic. Genetic linkage studies excluded linkage to the alpha-subunit of the skeletal muscle sodium channel and to four distinct LQT loci. In addition, none of the common dihydropyridine receptor mutations responsible for hypokalemic periodic paralysis were present. We conclude that (1) AS is a genetically unique channelopathy affecting both cardiac and skeletal membrane excitability, (2) attacks of paralysis may be either hypokalemic or hyperkalemic, (3) a prolonged QT interval is an integral feature of this syndrome, and (4) a prolonged QT interval may be the only sign in an individual from an otherwise typical AS kindred. This may be confused with more common, potentially lethal LQT syndromes.

Adolescent↗
PubMed1996

Pharmacologic treatment of emotional lability.

Emotional lability may be a part of the syndrome of pseudobulbar palsy. Here we report our experience with fluvoxamine, a selective serotonin reuptake inhibitor, used to treat 10 patients with emotional incontinence. Over a 7-month period, we studied and treated 10 consecutive patients (mean age, 61 +/- 8 years) attending our department: four had amyotrophic lateral sclerosis (progressive bulbar palsy form), four had clinically definite multiple sclerosis, and two had had strokes. They were given a single evening dose (100 mg) of fluvoxamine. All 10 patients had > 30 affective outbursts daily. It was observed that in 2 to 6 days, all the patients improved, the number of emotional outbursts dropping to none to five per day. This result suggests that the serotoninergic system may be implicated in emotional lability. The short latency of improvement we observed in our patients suggests that the mechanism of fluvoxamine for treating emotional lability differs from its mechanism for treating affective disorders.

Affective Symptoms↗
PubMed1996

The impact of sleep deprivation on erotic erections.

OBJECTIVE AND METHODS: The audiovisual stimulation penogram seems to be an appropriate screening test for erectile failure. However, falsely abnormal findings in psychogenically impotent patients with severe excitement inhibition can be found. Since disinhibitory effects may occur after sleep deprivation, we evaluated RigiScan results during audiovisual stimulation before and after sleep deprivation in 36 psychogenically impotent men. RESULTS: In our patients, sleep deprivation induced an increase in penile tumescence and rigidity before intracavernous injection of prostaglandin E1 as well as after the injection. CONCLUSION: Our data suggest that sleep deprivation combined with vascular testing and visual stimulation might lead to more precise diagnosis in male impotence.

Adult↗
PubMed1995

Evidence of peripheral axonal neuropathy in primary restless legs syndrome.

Restless legs syndrome (RLS) is a well-defined clinical entity characterized by an unpleasant creeping sensation arising in the legs with an irresistible need to move them. The trouble is more pronounced when the affected people lie in a prolonged rest position and try to fall asleep. It is known that RLS may be consequent to systemic disorders and to diseases affecting the central or peripheral nervous system. The International Classification of Sleep Disorders states that peripheral neuropathy should be ruled out by medical history and clinical grounds before diagnosing primary RLS (pRLS). The present study extended peripheral nerve investigation in eight consecutive pRLS patients with normal neurological examination results and showed that all patients exhibited two or more electrical, psychophysiological, and/or morphological features of peripheral axonal neuropathy. Morphometric analysis of sural nerve showed a significant reduction in myelinated fiber density and g ratio (axon diameter/fiber diameter) in the pRLS group compared with eight control biopsy specimens. These results suggest that axonal neuropathy is often present in patients with RLS. A comprehensive peripheral nerve investigation should be considered in RLS patients.

Adult↗
PubMed1995

Variable response of the Mongolian gerbil to unilateral carotid occlusion: magnetic resonance imaging and neuropathological characterization.

In the present investigation, we estimated both the evolution and the severity of ischemic damage following unilateral carotid occlusion (UCO) in Mongolian gerbils by using conventional magnetic resonance imaging (MRI, i.e. T2 weighted imaging) and histological techniques. Immediately after UCO, the animals showed different clinical effects. The mortality (46%) detected within the first 48h was considered an "stroke-sensitivity", the "stroke-resistant" animals showed wide variability in terms of both temporal evolution and the extent of ischemic damage. The signal hyperintensity and negative MRI observed during the first 30h after UCO did not always correlate with the cerebral damage presented after 14 days, although a close correlation was established between the T2 weighted images taken more than 30h after UCO and neuropathology: the gerbils negative to imaging showed no morphological changes, whereas an enhanced signal was always prognostic of ischemic injury. Moreover, late MRI documented ventricular dilatation. Histopathology showed that the ischemic damage differed among the stroke-resistant gerbils and was often bilateral. The present study confirms the differences in gerbil susceptibility to hemispheric infarction after permanent UCO and suggests that conventional MRI may be a useful non-invasive method for i) identifying the stroke-resistant animals prone to mature ischemic injury and ii) monitoring the evolution of therapeutic efficacy without sacrificing animals.

Animals↗