Suicide after successful deep brain stimulation for movement disorders.
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Adult↗
Biomedical subjects
S Piacentini
Publications and source records attributed to S Piacentini.
Brainstem neurodegeneration correlates with clinical dysfunction in SCA1 but not in SCA2. A quantitative volumetric, diffusion and proton spectroscopy MR study.
Magnetic resonance (MR) techniques enable in vivo measurement of the atrophy of the brainstem and cerebellum in spinocerebellar ataxia type 1 (SCA1) and 2 (SCA2) patients, which is accompanied by a decrease in the concentration of N-acetyl aspartate (NAA) or of the NAA/creatine ratio in the pons and cerebellum. Mean diffusivity (D) is emerging as an additional sensitive and quantitative MR parameter to investigate brain diseases. In order to explore differences between the MR features of SCA1 and SCA2 and correlate the MR and clinical findings in the two conditions, we examined 16 SCA1 patients, 12 SCA2 patients and 20 healthy control subjects. The MR protocol included T1-weighted 3D gradient echo sequences, single-voxel proton spectroscopy of the right cerebellar hemisphere (dentate and peridentate region) and of the pons with a PRESS sequence and an external reference quantitation method, and (in nine patients with SCA1 and nine patients with SCA2) diffusion-weighted echo-planar images with reconstruction of the D maps. The patients were evaluated with the Inherited Ataxia Clinical Rating Scale (IACRS). Compared with control subjects, the SCA1 and SCA2 patients showed a decrease (P < 0.01) in the volume of the brainstem and cerebellum and in the concentration of NAA in the pons and cerebellar hemisphere, whereas D of the brainstem and cerebellum was increased. No significant difference was observed between the SCA1 and SCA2 patient groups. No correlation between cerebellar volume and dentate and peridentate NAA concentration was found in SCA1 or SCA2 patients. The volume of the brainstem, D of the brainstem and cerebellum and the concentration of NAA in the pons were correlated (P < 0.05) with the IACRS score in SCA1 but not in SCA2. This discrepancy is in line with the clinical observation that the clinical deficit has a later onset and faster progression in SCA1 and an earlier onset and slower progression in SCA2, and suggests that neurodegeneration of the brainstem is a comparatively more rapid process in SCA1. In conclusion, our study indicates that SCA1 and SCA2 substantially exhibit the same MR features. The correlation in SCA1 between clinical severity and quantitative volumetric, diffusion MRI and proton MR spectroscopy findings in the brainstem indicates that these measurements might be employed for longitudinal studies and hopefully as surrogate markers in future pharmacological trials of this condition.
Adult↗
Ataxia with isolated vitamin E deficiency: neurological phenotype, clinical follow-up and novel mutations in TTPA gene in Italian families.
Ataxia with vitamin E deficiency (AVED) is a rare autosomal recessive neurodegenerative disorder due to mutations in the alpha-tocopherol transfer protein (TTPA) gene on chromosome 8q13. AVED patients have progressive spinocerebellar symptoms and markedly reduced plasma levels of vitamin E. We studied neurological phenotype at diagnosis, and long-term effect of vitamin E supplementation in 16 patients from 12 Italian families. The most common mutations were the 744delA and 513insTT. Two novel TTPA mutations were identified: a severe truncating mutation (219insAT) in a homozygous patient, and a Gly246Arg missense mutation (G246R) in a compound heterozygous patient. The missense mutation was associated with a mild and slowly progressive form of the disease. Vitamin E supplementation therapy allowed a stabilization of the neurological conditions in most of the patients. However, development of spasticity and retinitis pigmentosa was noted in a few patients during therapy. Prompt genetic characterization of AVED patients may allow an effective early treatment and an adequate genetic counseling.
Adolescent↗
Progressive dysarthria: definition and clinical follow-up.
Progressive dysarthria is a common sign of several degenerative disorders of the central nervous system; it may also be a distinct nosographic entity. We identified nine patients in which progressive dysarthria remained the sole neurological sign for at least 2 years after onset. At least a year after hospital admission, the following diagnoses were made: two cases of corticobasal degeneration, one of frontotemporal dementia, one of primary progressive aphasia, one of motor neuron disease (MND)-dementia, one of ALS, and one of ALS-aphasia. In the remaining two patients progressive dysarthria remained the only neurological sign at latest examination. We conclude that in most cases progressive dysarthria is the presenting sign of an established neurodegenerative disease (generally degenerative dementia or motor neuron disease), although the possibility that progressive dysarthria is a distinct entity cannot be excluded. To clarify this issue, studies (probably multicenter) on more patients with longer clinical follow-up and pathological confirmation are required.
Amyotrophic Lateral Sclerosis↗
Distal-proximal differences in limb apraxia in corticobasal degeneration but not progressive supranuclear palsy.
Limb apraxia is an important diagnostic sign of cortico-basal degeneration (CBD), although it is also found in progressive supranuclear palsy (PSP). We investigated whether the severity of apraxia differed between proximal and distal arm movements in the two diseases, as suggested by their differing patterns of motor impairment. We studied 24 CBD patients, 25 PSP patients, and 19 healthy controls using a battery of cognitive tests and an ideomotor apraxia test that examined imitation of hand and of whole arm gestures separately. CBD and PSP patients did not differ in general characteristics or disability and were similarly impaired in cognitive performance. Within-group differences between distal and proximal gesture scores were significant only for CBD patients ( p=0.007), in whom distal movements were more compromised. This finding suggests the presence of limb kinetic apraxia in CBD, perhaps in association with ideomotor apraxia.
Activities of Daily Living↗
A study of arm movements in Huntington's disease under visually controlled and blindfolded conditions.
The so-called bradykinesia of Huntington's disease (HD) seems not due to reduced movement speed alone but may also be task-dependent. We therefore investigated the influence of visual control on the ability of HD patients to perform a motor task. Ten HD patients, never treated with neuroleptic drugs and with mild functional impairment in activities of daily living, performed the task blindfolded and not blindfolded, as did 10 age- and education-matched healthy controls. The task was to use the dominant hand to trace out the contours of a 20 x 20 cm square in a clockwise direction, pausing at each corner. The square was marked on the table at which the subject sat. Accuracy was stressed rather than speed. A videocamerabased system recorded movement trajectories, from which kinematic and error parameters were derived. Patients and controls moved at comparable speeds but patients took longer to complete the task due to more curvilinear and hence longer trajectories. Patients spent more time in the deceleration phase of the movement, and in the blindfold condition had more variable movements as indicated by greater error variability scores. Correlation analysis showed that kinematic parameters in patients did not correlate with involuntary movement scores. These findings indicate that abnormalities of motor control are present in HD when movement accuracy (and not velocity) is required. HD patients are more dependent on visual control than normal subjects.
Adult↗
Safety and tolerability of cyclophosphamide 'pulses' in multiple sclerosis: a prospective study in a clinical cohort.
To assess the safety and tolerability of cyclophosphamide (CTX) 'pulse' therapy in progressive or very active multiple sclerosis (MS), we reviewed our experience in a cohort of MS patients who have been treated and prospectively followed-up in our Department since 1997. One hundred and twelve patients received intravenous CTX in monthly 'pulses' for 12 months at the dosage of 700 mg/m2 of body surface, then bimonthly for another 12 months. We evaluated the frequency and the severity of side-effects, as well as overall tolerability by the patient perspective using a visual analogue scale (VAS). Side-effects resulted in the discontinuation of therapy in 20 (18%) cases. Serious side-effects were observed in 24 patients (21.4%), most commonly definitive amenorrhea (33.3% of fertile women), hypogammaglobulinemia (5.4%), and hemorrhagic cystitis (4.5%). Malignancies were diagnosed in four (3.6%) subjects, three of whom were previously treated with azathioprine (AZA). Finally, 81.8% of the patients judged the treatment regimen as very or relatively acceptable and tolerable. Our data point to a reasonable safety and tolerability of CTX 'pulse' therapy. Further trials are needed to definitively assess the efficacy of CTX as an alternative therapeutic option for progressive or very active MS.
Adult↗
Cognitive and psychiatric characterization of patients with Huntington's disease and their at-risk relatives.
We examined cognitive and psychiatric disturbances in patients with Huntington's disease (HD) in comparison to at-risk asymptomatic subjects. Cognitive and psychiatric scales and an HD motor scale were administered to 40 HD patients, 17 pre-symptomatic HD gene carriers (AR+) and 28 non gene carriers (AR-). HD patients did worse than AR+ and AR- in all motor, cognitive and psychiatric measures, while AR+ and AR-subjects did not differ between each other. HD patients had high scores for negative psychiatric symptoms, but there was no correlation between illness duration and psychiatric or cognitive performance. In HD, disease course and symptomatology are heterogeneous and negative psychiatric symptoms are common.
Adult↗
Association between 5-HT(2A) receptor polymorphism and psychotic symptoms in Alzheimer's disease.
BACKGROUND: The aim of this study is to analyze the segregation of the 102T/C polymorphism in the serotonin 2A receptor gene in patients affected by sporadic and familial Alzheimer's disease (FAD) with and without psychotic symptoms. METHODS: The polymorphism was analyzed in 275 subjects. A semistructured interview was used to obtain information about delusions, hallucinations, and other specific behavioral signs occurring during the disease. RESULTS: Fifty-two percent of AD patients with psychotic symptoms were homozygous for the C102 allele, as compared with 6.9% of AD patients without psychosis. Similarly, the C102/C102 genotype was significantly more frequent in FAD patients with psychosis than in FAD patients without (46.5% vs. 7.8%). CONCLUSIONS: Our data strongly confirm and extend to FAD previous studies suggesting that the genetic variation at this locus is associated with prominent psychotic features in AD and that the 102C allele could play an important role in late-onset AD.
Aged↗
Genetic and clinical analysis of spinocerebellar ataxia type 8 repeat expansion in Italy.
BACKGROUND: The spinocerebellar ataxias (SCAs) are clinically heterogeneous disorders caused by triplet repeat expansions in the sequence of specific disease genes. Spinocerebellar ataxia type 8 (SCA8), originally described in a family characterized by pure cerebellar ataxia with slow disease progression, presents with expansion of combined CTA/CTG repeats. OBJECTIVE: To perform SCA8 repeat expansion analysis in a heterogeneous group of ataxic patients, to determine the prevalence of this mutation in our patients and establish the frequency of expanded CTA/CTG repeats in a large group of control subjects. PATIENTS: One hundred sixty-seven patients affected by sporadic, autosomal dominant and recessive hereditary ataxia were clinically examined and analyzed for SCA8 expansion. We further studied 161 control subjects and 125 patients with psychiatric disorders. RESULTS: We found abnormally expanded CTA/CTG repeats in 5 ataxic patients, 3 of them characterized by pure cerebellar ataxia. One patient had vitamin E deficiency and 1 patient with a sporadic case was affected by gluten ataxia. No evidence of expanded alleles was found in healthy control subjects and in patients with psychiatric disorders. CONCLUSIONS: Our data support the evidence that CTG expansions may be linked to SCA8, since the pathogenic expansions have been found only among patients with genetically unidentified forms of hereditary and sporadic ataxia. Patients carrying expanded alleles present peculiar phenotypic features, thus suggesting that unknown additional factors could probably predispose to the disease.
Adult↗
Acute effects of bilateral subthalamic nucleus stimulation on clinical and kinematic parameters in Parkinson's disease.
After implantation with subthalamic stimulators, nine patients with advanced Parkinson's disease were studied on the task of tracing out, as accurately as possible, the four corners of a square with the dominant hand. The task was performed in four treatment conditions: on stimulation-off medication, off stimulation-off medication, off stimulation-on medication, and on stimulation-on medication. Movement times and peak velocities improved significantly only in the on stimulation-on medication condition compared to off stimulation-off medication. The improvement in clinical parameters with stimulation only (relative to off stimulation off medication) was of borderline significance, while consistent and significant clinical improvement was only obtained with addition of medication (on medication-on stimulation). This study provides quantitative evidence of the effect of subthalamic stimulation on kinematic measures in Parkinson's disease (PD) and suggests that combined treatment (medication and stimulation) is superior to either treatment alone.
Aged↗
Psychosis, serotonin receptor polymorphism and Alzheimer's disease.
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Journal Article↗
A presenilin-1 mutation (Leu392Pro) in a familial AD kindred with psychiatric symptoms at onset.
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Adult↗
Atypical Friedreich ataxia with a very late onset and an unusual limited GAA repeat.
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Age Factors↗
Risperidone in idiopathic and symptomatic dystonia: preliminary experience.
Risperidone is a heterocyclic neuroleptic with prominent antiserotoninergic (5HT2) as well as antidopaminergic (D2) activity. We studied the efficacy of risperidone in the treatment of idiopathic and symptomatic dystonias in seven patients using the Fahn and Marsden rating scale for torsion dystonia before and after four weeks of treatment (2-6 mg/day). The twisting and involuntary movements with abnormal postures decreased in all the patients treated, with a statistically significant mean improvement (41%; p = 0.009, CI 95%). Our results suggest that risperidone is useful in idiopathic and symptomatic dystonia.
Adolescent↗
Implication of alpha1-antichymotrypsin polymorphism in familial Alzheimer's disease.
A common polymorphism in the alpha1-antichymotrypsin (ACT) gene has been shown to modify the Apolipoprotein E (ApoE) epsilon4-associated Alzheimer's disease (AD) risk identifying the combination of the ACT/AA and ApoE epsilon4/epsilon4 genotypes as a potential susceptibility marker for AD. Using the polymerase chain reaction, we analyzed the segregation of the ACT and ApoE polymorphisms in familial Alzheimer's disease (FAD) patients carrying mutations in Presenilin (PS) and APP genes and in both early onset (EO) and late onset (LO) FAD patients without known mutations. Our data suggest that ACT does not represent an additional risk factor for PS and APP mutated families. However, in LOFAD patients a high frequency of the combined ACT/AA and ApoE epsilon4/epsilon4 genotypes suggest that ACT may interact with ApoE and play a role in LOFAD.
Adult↗
No implication of apolipoprotein E polymorphism in Italian schizophrenic patients.
Numerous studies have provided evidence for a genetic association of the Apolipoprotein E (ApoE) epsilon4 allele and late onset familial and sporadic Alzheimer's disease (AD). Clinical observations show that a proportion of schizophrenic patients may suffer from severe cognitive impairment. That could reflect a particular clinical aspect of this mental disorder or a common, yet unknown, neurodegenerative mechanism. We analysed the ApoE gene polymorphism in a sample of 69 Italian patients with schizophrenia, 140 AD patients and 121 controls. In schizophrenic patients, the distribution of ApoE genotypes does not significantly differ from that of controls. No effect of the ApoE genotype on age of onset was found. The frequency of ApoE alleles in Italian schizophrenic patients is comparable with control values, suggesting that ApoE polymorphism does not represent a risk factor for schizophrenia.
Age of Onset↗
Inherent abnormalities in oxidative metabolism in Alzheimer's disease: interaction with vascular abnormalities.
Extensive studies over the last 20 years have documented the existence of inherent abnormalities in oxidative/energy metabolism in Alzheimer's disease (AD). These abnormalities can be linked to characteristics of AD by plausible pathophysiological mechanisms for which there is abundant, robust evidence. The inherent abnormalities in cerebral metabolism of oxygen and glucose can reasonably be expected to interact synergistically with vascular compromise of cerebral oxygen and glucose metabolism in causing brain damage in AD.
Alzheimer Disease↗