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G Rizzo,
D Manners,
R Vetrugno,
C Tonon,
E Malucelli,
G Plazzi,
S Marconi,
F Pizza,
C Testa,
F Provini, P Montagna,
R Lodi
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ABSTRACT: The aim of this study was to evaluate the presence of abnormalities in the brain of patients with restless legs syndrome (RLS) using voxel-based morphometry and diffusion tensor imaging (DTI).
Twenty patients and twenty controls were studied. Voxel-based morphometry analysis was performed using statistical parametric mapping (SPM8) and FSL-VBM software tools. For voxel-wise analysis of DTI, tract-based spatial statistics (TBSS) and SPM8 were used.
Applying an appropriate threshold of probability, no significant results were found either in comparison or in correlation analyses.
Our data argue against clear structural or microstructural abnormalities in the brain of patients with idiopathic RLS, suggesting a prevalent role of functional or metabolic impairment.
European Journal of Neurology 12/2011; 19(7):1045-9. · 3.69 Impact Factor
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ABSTRACT: Myotonic dystrophy type 1 (DM1) is a multisystem disorder. Many tests in the literature have evaluated single aspects of DM1 patients, mainly focusing on muscular impairment, without an overall quantification of the different disease-specific neurological features. We developed and validated a new functional scale for DM1 patients based on neuromuscular impairment (NI) and disability.
Thirty-three patients were tested in basal condition, 18 were re-evaluated after therapeutic intervention with mexiletine, and 13 at one year follow-up without treatment. The scale includes 21 ordinal items in four areas: neuropsychology, motricity, myotonia and daily life activities. We evaluated inter- and intra-observer reliability (intraclass correlation coefficient, ICC and Spearman correlations, respectively), internal consistency (Cronbach's alpha), external validity (Spearman correlations between each area and other clinical and objective measurements and scales), and sensitivity to clinical changes after treatment or at follow-up.
Our analysis provided good results for inter-observer agreement (ICC = 0.72-0.97), intra-observer reliability, and internal consistency for all areas (Cronbach's α > 0.73). Total score and single area subscores were significantly correlated to objective measurements, disease duration and multisystem involvement. Finally, the scale was sensitive to clinical changes disclosing a significant improvement after treatment in the items assessing myotonia, and also to disease progression showing a significant worsening in all areas but myotonia in untreated patients.
Our scale provides a new practical measure to evaluate NI and disability of DM1 patients. Further longitudinal studies are warranted to confirm its reliability in tracking disease progression and severity over a longer period of time.
Acta Neurologica Scandinavica 09/2011; 125(6):431-8. · 2.47 Impact Factor
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ABSTRACT: To determine clinical and laboratory predictors of restless legs syndrome (RLS) in patients with end-stage kidney disease (ESKD) undergoing long-term hemodialysis (HD).
One hundred and sixty-two consecutive patients were assessed. History of sleep disturbances, neurological examination, clinical, and laboratory data were collected. Patients with and without RLS were compared, and a logistic regression model described the relations between independent predictors and RLS.
Fifty-one patients (32%) currently had RLS (RLS+). RLS+ vs RLS- patients were more frequently women (49% vs 29%, P = 0.012), had first-degree relative with RLS (22% vs 6%, P = 0.004), insomnia (59% vs 36%, P = 0.007), peripheral neuropathy (41% vs 21%, P = 0.006), and low residual diuresis (92% vs 68% with below 500 ml/24 h, P = 0.001). Low (OR = 8.71, CI = 2.27-33.41; P = 0.002) and absent (OR = 4.96, CI = 1.52-16.20; P = 0.008) residual diuresis, peripheral neuropathy (OR = 4.00, CI = 1.44-11.14; P = 0.008), and first-degree relative with RLS (OR = 3.82, CI = 1.21-12.13; P = 0.023) significantly predicted RLS in ESKD patients undergoing HD.
Positive family history for RLS together with reduced/absent residual renal function and peripheral neuropathy predicts the risk for RLS in ESKD patients undergoing HD. Longitudinal studies are warranted to correlate RLS occurrence with genetic and environmental factors.
Acta Neurologica Scandinavica 08/2011; 125(6):403-9. · 2.47 Impact Factor
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Handbook of Clinical Neurology 01/2011; 99:883-99.
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V Donadio,
P Cortelli,
M Elam,
V Di Stasi, P Montagna,
B Holmberg,
M P Giannoccaro,
E Bugiardini,
P Avoni,
A Baruzzi,
R Liguori
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ABSTRACT: Pure autonomic failure (PAF) and multiple system atrophy (MSA) are both characterised by chronic dysautonomia although presenting different disability and prognosis. Skin autonomic function evaluation by indirect tests has revealed conflicting results in these disorders. Here, the authors report the first direct analysis of skin sympathetic fibres including structure and function in PAF and MSA to ascertain different underlying autonomic lesion sites which may help differentiate between the two conditions.
The authors studied eight patients with probable MSA (mean age 60±5 years) and nine patients fulfilling diagnostic criteria for PAF (64±8 years). They underwent head-up tilt test (HUTT), extensive microneurographic search for muscle and skin sympathetic nerve activities from peroneal nerve and punch skin biopsies from finger, thigh and leg to evaluate cholinergic and adrenergic autonomic dermal annexes innervation graded by a semiquantitative score presenting a high level of reliability.
MSA and PAF patients presented a comparable neurogenic orthostatic hypotension during HUTT and high failure rate of microneurographic trials to record sympathetic nerve activity, suggesting a similar extent of chronic dysautonomia. In contrast, they presented different skin autonomic innervation in the immunofluorescence analysis. MSA patients showed a generally preserved skin autonomic innervation with a significantly higher score than PAF patients showing a marked postganglionic sympathetic denervation. In MSA patients with a long disease duration, morphological abnormalities and/or a slightly decreased autonomic score could be found in the leg reflecting a mild postganglionic involvement.
Autonomic innervation study of skin annexes is a reliable method which may help differentiate MSA from PAF.
Journal of neurology, neurosurgery, and psychiatry 12/2010; 81(12):1327-35. · 4.87 Impact Factor
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ABSTRACT: The migraine attack is a reversible brain dysfunction characterized by pain autonomic symptoms and passive coping strategies consistent with sickness behavior. The migraine attack may be interpreted as an example of genetically determined adaptive behavioral response to internal or external stressors that it is orchestrated by a threatened brain. In this view, the migraine attack itself may not be categorized as a disease, i.e., a deviation from or interruption of the normal structure or function of the brain but it may turn into a disease in an allostatic perspective, when the repeated migraine attacks start maladaptive mechanisms (inefficient turning on or shutting off of the mechanisms underlying the migraine attack) that resulted in a chronic pain of the brain. In future, we should recognize and treat early all the conditions able to transform a normal response of the brain into a morbid state, i.e., we have to categorize migraine not only as a type of headache attack but also as a symptom of different syndromes.
Neurological Sciences 06/2010; 31 Suppl 1:S29-31. · 1.32 Impact Factor
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ABSTRACT: Migraine attacks have a seasonal, menstrual and circadian periodicity, suggesting a role of chronobiological mechanisms probably related to a hypothalamic involvement. The aim of the study was to evaluate the chronotypes in patients with menstrual migraine, a migraine sub-type with a cyclical recurrence compared to normal female. Ninety-three patients with ICHD-II diagnosis of pure menstrual migraine and menstrually-related migraine were recruited and compared to 85 age-matched healthy women. The Italian version of Morningness-Eveningness Questionnaire was administered to identify circadian preference of our participants. No differences were found regarding the distribution of chronotypes in patients with menstrual migraine and healthy controls. The study did not confirm the presence of a morning and evening preference among migraineurs as previously reported.
Neurological Sciences 06/2010; 31 Suppl 1:S163-4. · 1.32 Impact Factor
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ABSTRACT: We investigated the prevalence of nocturnal smoking (NS) in patients with RLS.
One hundred RLS patients living in Emilia-Romagna (Northern Italy) and 100 matched controls, randomly selected from the general population, underwent interviews for the presence of nocturnal smoking and for obsessive-compulsive traits, depression, excessive daytime sleepiness (EDS) and subjective sleep quality.
NS was more prevalent in RLS patients than controls (lifetime prevalence: 12% vs. 2%, P=0.012). Patients with NS had more frequently Sleep-Related Eating Disorders (SRED) than patients without NS (83.3% vs. 26.1%, P=0.0002). Pathological and borderline Maudsley Obsessive-Compulsive Inventory (MOCI) values as well as pathological values at the Beck Depression Inventory (BDI) increased from controls to RLS patients without NS to RLS patients with NS (P=0.005 and P=0.01, respectively).
We demonstrate an increased prevalence of NS in patients with RLS, in many cases associated with increased SRED. NS may be associated with psychopathological traits in RLS and may be relevant in the management of RLS patients.
Sleep Medicine 02/2010; 11(2):218-20. · 3.40 Impact Factor
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ABSTRACT: To test the autonomic control of cardiovascular reflexes and heart rate variability (HRV) at rest and during orthostatic stress in narcolepsy with cataplexy (NC).
Ten NC patients with a hypocretin deficit and 18 control subjects underwent head-up tilt test (HUTT), Valsalva manoeuvre, deep breathing and cold face under controlled laboratory conditions. Heart rate variability (HRV) was analysed during supine rest and HUTT considering the normalized unit of LF and HF power (LFnu; HFnu), using autoregressive (AR) and fast Fourier transform (FFT) algorithms.
Cardiovascular changes during HUTT, Valsalva manoeuvre, deep breathing, isometric handgrip and cold face were normal and comparable in the two groups. AR and FFT analysis showed an increased LF/HF ratio in NC patients during supine rest. As expected, LFnu increased and HFnu decreased in the control group during HUTT, but did not change in narcoleptics being comparable to values in the supine condition.
NC patients showed an increased sympathetic drive on heart rate (HR) in the supine condition that did not further increase during HUTT.
These results suggest the proper functioning of cardiovascular reflexes in NC but support an impairment of HR modulation at rest in favour of an enhanced sympathetic activity.
Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 02/2010; 121(7):1142-7. · 3.12 Impact Factor
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Journal of neurology, neurosurgery, and psychiatry 01/2010; 81(1):122-3. · 4.87 Impact Factor
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D Grimaldi,
C Tonon,
S Cevoli,
G Pierangeli,
E Malucelli,
G Rizzo,
S Soriani, P Montagna,
B Barbiroli,
R Lodi,
P Cortelli
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ABSTRACT: We used multimodal magnetic resonance (MR) techniques [brain diffusion-weighted magnetic resonance imaging, diffusion-weighted imaging (DWI), proton MR spectroscopy (MRS), (1)H-MRS; and skeletal muscle phosphorous MRS, (31)P-MRS] to investigate interictal brain microstructural changes and tissue energy metabolism in four women with genetically determined familial hemiplegic migraine type 2 (FHM2), belonging to two unrelated families, compared with 10 healthy women. Brain DWI revealed a significant increase of the apparent diffusion coefficient median values in the vermis and cerebellar hemispheres of FHM2 patients, preceding in two subjects the onset of interictal cerebellar deficits. (31)P-MRS revealed defective energy metabolism in skeletal muscle of FHM2 patients, while brain (1)H-MRS showed a mild pathological increase in lactate in the lateral ventricles of one patient and a mild reduction of cortical N-acetyl-aspartate to creatine ratio in another one. Our MRS results showed that a multisystem energy metabolism defect in FHM2 is associated with microstructural cerebellar changes detected by DWI, even before the onset of cerebellar symptoms.
Cephalalgia 09/2009; 30(5):552-9. · 3.43 Impact Factor
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V Donadio, P Montagna,
M Pennisi,
R Rinaldi,
V Di Stasi,
P Avoni,
E Bugiardini,
M P Giannoccaro,
P Cortelli,
G Plazzi,
A Baruzzi,
R Liguori
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ABSTRACT: Agrypnia Excitata (AE) is characterized by autonomic over-activity and cardiovascular fluctuations but direct evidence of sympathoexcitation is lacking. AE is a common feature of acquired (i.e. Morvan's syndrome--MS) and genetic (i.e. fatal familial insomnia--FFI) conditions where a dysfunction of the thalamo-limbic system has been suggested. The aim of this study is to report the first microneurographic recordings of sympathetic activity in acquired and genetic AE to investigate the pattern of sympathetic activation.
We describe two patients presenting acquired AE (MS) as demonstrated by elevated serum antibody levels to voltage-gated potassium channels and one patient with genetically confirmed FFI. Patients and fifteen sex and age-matched healthy controls underwent microneurography from peroneal nerve to assess muscle sympathetic nerve activity (MSNA) and heart rate (HR).
Mean level of resting awake MSNA and HR was significantly increased in patients compared to controls. Patients presented a similar pattern of MSNA with a normal cardiac rhythmicity and a very high burst incidence expressed in approximately each cardiac beat.
Acquired and genetic AE presented a resting awake sympathetic over-activity.
AE patients may develop high blood pressure and/or cardiovascular instability potentially increasing the morbidity/mortality of the underlying disorders.
Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 06/2009; 120(6):1139-42. · 3.12 Impact Factor
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D N Manners,
P Parchi,
C Tonon,
S Capellari,
R Strammiello,
C Testa,
G Tani,
E Malucelli,
C Spagnolo,
P Cortelli, P Montagna,
R Lodi,
B Barbiroli
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ABSTRACT: The cause of hyperintense magnetic resonance changes and reduced apparent diffusion coefficient (ADC) in specific brain regions of patients with Creutzfeldt-Jakob disease (CJD) is unknown. Our aim was to determine the neuropathologic correlates of antemortem water ADC and normalized T2-weighted changes in patients with CJD.
Ten patients with CJD and 10 sex- and age-matched healthy controls were studied by DWI and T2-weighted echoplanar MRI. At postmortem, patients with CJD were evaluated for semiquantitative assessment of gliosis and neuronal loss, spongiform changes, and abnormal PrP protein deposition in four cortical regions (occipital, parietal, and temporal cortex, and cingulate gyrus), thalamus, and striatum for a total of 60 regions of interest (ROI).
Gliosis and neuronal loss correlated very highly with each other in the 60 ROIs. Where status spongiosus was absent, spongiform change correlated very highly with gliosis and neuronal loss in the cortex, but not in deep gray matter. Spongiform change was also significantly correlated with PrPSc load in both cortical and deep gray ROIs. In deep gray matter, ADC decreased with increasing spongiform change (R2 = 0.78; p < 0.001) and PrPSc load (R2 = 0.51; p = 0.003). In the cortex, ADC decreased with increases in all three, highly correlated, pathologic scores.
Antemortem reductions in ADC values, typically found in patients with Creutzfeldt-Jakob disease (CJD), are correlated with spongiform changes seen at autopsy. This could be clearly established in the striatum and thalamus of our patients with CJD where the extent of spongiform change was not significantly correlated with gliosis or neuronal loss.
Neurology 05/2009; 72(16):1425-31. · 8.31 Impact Factor
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T Pippucci,
E Panza,
E Pompilii,
V Donadio,
A Borreca,
C Babalini,
C Patrono,
R Zuntini,
T Kawarai,
G Bernardi,
R Liguori,
G Romeo, P Montagna,
A Orlacchio,
M Seri
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ABSTRACT: Autosomal Recessive Hereditary Spastic Paraplegia with Thin Corpus Callosum (AR-HSPTCC) is a clinically and genetically heterogeneous complicated form of spastic paraplegia. Two AR-HSPTCC loci have been assigned to chromosome 15q13-15 (SPG11) and chromosome 8p12-p11.21 respectively. Mutations in the SPG11 gene, encoding the spatacsin protein, have been found in the majority of SPG11 families. In this study, involvement of the SPG11 or 8p12-p11.21 loci was investigated in five Italian families, of which four consanguineous.
Families were tested for linkage to the SPG11 or 8p12-p11.21 loci and the SPG11 gene was screened in all the affected individuals.
Linkage was excluded in the four consanguineous families. In the only SPG11-linked family the same homozygous haplotype 4.2 cM across the SPG11 locus was shared by all the three affected siblings. A novel c.2608A>G mutation predicted to affect the splicing was found in exon 14 of the SPG11 gene.
This collection of families contributes to highlight the intra and inter locus heterogeneity in AR-HSPTCC, already remarked in previous reports. In particular, it confirms heterogeneity amongst Italian families and reports a new mutation predicted to affect splicing in the spatacsin gene.
European Journal of Neurology 01/2009; 16(1):121-6. · 3.69 Impact Factor
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Autonomic Neuroscience-basic & Clinical - AUTON NEUROSCI-BASIC CLIN. 01/2009; 149(1):67-68.
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Neurology 11/2008; 71(18):1452-4. · 8.31 Impact Factor
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ABSTRACT: Fatal familial insomnia, a human prion disease, Morvan's chorea, an autoimmune limbic encephalopathy, and delirium tremens, the well-known alcohol (or benzodiazepine [BDZ]) withdrawal syndrome, share a clinical phenotype largely consisting in an inability to sleep associated with motor and autonomic activation. Agrypnia excitata is the term which aptly defines this clinical condition, whose pathogenetic mechanism consists in an intralimbic disconnection releasing the hypothalamus and brainstem reticular formation from corticolimbic inhibitory control. Severance of cortical-subcortical limbic structures is due to visceral thalamus degeneration in fatal familial insomnia, and may depend on autoantibodies blocking voltage-gated potassium channels within the limbic system in Morvan's chorea, and the sudden changes in gabaergic synapses down-regulated by chronic alcohol abuse within the limbic system in delirium tremens. On the basis of these findings, we suggest that a neuronal network, extending from the medulla to the limbic cortex, controls the sleep-wake cycle, operating in an integrated fashion following a caudorostral organization.
Revue Neurologique 10/2008; 164(8-9):692-700. · 0.49 Impact Factor
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ABSTRACT: Ross syndrome is characterised by tonic pupil, areflexia and anhidrosis, and the underlying lesion affects postganglionic skin sympathetic nerve fibres. We describe a 51-year-old man who had complained of anhidrosis since adolescence, at which time this problem was limited to the lower arms. The thermoregulatory sweating test disclosed generalised anhidrosis (GA) except for two small skin areas that were located in the right palm and left neck. Immunofluorescence analysis disclosed no cholinergic sudomotor fibres around the sweat glands of non-sweating skin areas, which were evident although sparse and deranged in the sweating site. In our patient, GA was induced by degeneration of postganglionic sympathetic skin nerve fibres, as found in Ross syndrome, although his clinical picture was incomplete as it lacked tonic pupil and areflexia. Isolated GA induced by degeneration of postganglionic sympathetic nerve fibers, directly evaluated by skin biopsy, has not previously been described.
Journal of neurology, neurosurgery, and psychiatry 09/2008; 79(8):959-61. · 4.87 Impact Factor
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E Panza,
T Pippucci,
R Cusano,
C Lo Nigro,
L Pradella,
S Contardi,
G A Rouleau,
G Stevanin,
R Ravazzolo,
R Liguori, P Montagna,
G Romeo,
M Seri
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ABSTRACT: The hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative disorders, characterized by a progressive spasticity of the lower limbs. So far, 33 different loci (SPGs) have been mapped and the 15 genes responsible have been identified. We mapped a locus responsible for a form of spastic paraplegia, complicated by bilateral cataracts, gastroesophageal reflux with persisting vomiting and amyotrophy to chromosome 10q23.3-q24.2, in an Italian family. The critical region was in a 12 cm chromosomal interval between markers D10S564 and D10S603 (SPG9, MIM601162). In the same region, two other forms of HSP have been recently mapped: SPG27 and SPG33. In the latter case, the gene responsible has been identified.
To better characterize this region, we genotyped individuals from SPG9-linked families using additional markers and reduced the candidate region to a 4.8 Mb, excluding several genes by positional cloning.
The refined SPG9 locus is positioned completely within SPG27 and does not include the SPG33 gene.
Fifty-two transcripts are present in the refined critical region and 25 strong candidates have been excluded as disease causing genes by direct sequencing. Six of them were also excluded as responsible for SPG27.
European Journal of Neurology 06/2008; 15(5):520-4. · 3.69 Impact Factor
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Journal of neurology, neurosurgery, and psychiatry 05/2008; 79(4):481-3. · 4.87 Impact Factor
