Biomedical subjects

Michele Tinazzi

Publications and source records attributed to Michele Tinazzi.

At least 19 recordsLinked to original sources

PubMed2007

Limb ataxia and proximal intracranial territory brain infarcts: clinical and topographical correlations.

BACKGROUND: Limb ataxia is classically attributed to cerebellar hemispheric lesions, although isolated lesions of the inferior cerebellar peduncle (ICP) in the medulla may also cause this sign. It is still unclear why only some patients with acute cerebellar infarcts in the posterior inferior cerebellar artery (PICA) territory present with limb ataxia. The proximal intracranial posterior circulation (P-PC) territory includes structures fed by the intracranial vertebral arteries (ICVAs): the medulla, supplied by small ICVAs branches, and posterior inferior portion of the cerebellum, fed by PICA. ICP and PICA territory cerebellar infarcts most often occur independently but occasionally occur together. OBJECTIVE: To identify structures responsible for limb ataxia in acute P-PC brain infarcts, correlating clinical and topographical findings. METHODS: Sixteen patients (8 women) were included, aged 30-82 years (mean 62 years), with isolated acute strokes in the P-PC territory. RESULTS: The cases reported here indicate that limb ataxia in acute P-PC territory infarcts may be associated with damage to the ICP in the dorsolateral medulla, regardless of a hemispheric cerebellar lesion. In fact, among the nine patients with PICA stroke, limb ataxia was observed only in the two patients who also presented damage to the dorsolateral medulla involving the ICP. Of the seven patients with isolated dorsolateral medullary infarct, only five patients with ICP damage had limb ataxia. CONCLUSIONS: When correlating limb ataxia and acute P-PC infarcts, it is important to take into account the entire ICVA territory.

Adult↗

PubMed2006

Defective temporal processing of sensory stimuli in DYT1 mutation carriers: a new endophenotype of dystonia?

DYT1 primary torsion dystonia is an autosomal dominant movement disorder due to a 3-bp GAG deletion in the TOR1A gene, which becomes manifest in only 30-40% of mutation carriers. Investigating the factors regulating this reduced penetrance might add new insight into the mechanisms underlying the disease. The pathophysiology of dystonia has been related to basal ganglia dysfunctions that lead to the most prominent motor symptoms. However, subclinical sensory deficits have also been reported, particularly in adult-onset focal dystonia. Sensory abnormalities in different forms of sporadic dystonia have been revealed by using a psychophysical method, namely, the temporal discrimination threshold (TDT), quantified as the shortest time interval at which the two stimuli are perceived as separate. Little or no information about the presence of sensory abnormalities in DYT1 gene manifesting and non-manifesting carriers is available. With the aim of disclosing possible associations between sensory deficits and the DYT1 mutation, we assessed TDTs of DYT1 manifesting patients (n = 9); DYT1 non-manifesting relatives (n = 11); non-carrier relatives (n = 9); external control subjects (n = 11). Pairs of tactile, visual or visuo-tactile stimuli were delivered in blocked, counterbalanced order. Intervals between stimuli increased from 0 to 400 ms (in 10 ms steps). On each trial, subjects had to report whether stimuli occurred simultaneously or asynchronously. We measured the first out of three consecutive inter-stimulus intervals at which subjects recognized the two stimuli as temporally separated (TDT) and the first of three consecutive intervals at which they also reported correctly which stimulus in the pair preceded (or followed) the other temporal order judgment (TOJ). Results showed higher tactile and visuo-tactile TDTs and TOJs in DYT1 carriers, both manifesting and non-manifesting, compared with non-carrier relatives and with external control subjects (for all comparisons, P < 0.039). This finding indicates that the DYT1 mutation determines subclinical sensory alterations, which could be disclosed by a psychophysical task. Moreover, these results have the notable implication that sensory deficits in dystonia are not a mere consequence of abnormal movements, but they may even occur before overt clinical manifestations, representing a subclinical phenotype in DYT1 mutation carriers.

Adult↗

PubMed2006

Head trauma in primary cranial dystonias: a multicentre case-control study.

BACKGROUND: The relationship between prior trauma and primary adult-onset dystonia is not well understood. Previous uncontrolled observations and exploratory case-control studies have yielded contradictory results. OBJECTIVE: To analyse the association between cranial dystonia and prior head trauma. METHODS: An ad hoc multicentre case-control study was performed using a semistructured interview to collect detailed information on the history of head trauma before disease onset in five Italian tertiary referral centres for movement disorders. The presence of a history of head trauma and of post-traumatic sequelae (loss of consciousness, bone fractures, scalp/facial wounds) before disease onset was recorded from 177 patients with primary adult-onset cranial dystonia and from 217 controls with primary hemifacial spasm matched by age strata and sex. Differences between groups were assessed by Mann-Whitney U test and Fisher's exact test, and the relationship between prior head trauma and case/control status was analysed by multivariate logistic regression models. RESULTS: No association was found between vault/maxillofacial trauma and cranial dystonia. Most reported traumas occurred several years before disease onset. None of the main post-traumatic sequelae altered the chance of developing cranial dystonia compared with patients with primary hemifacial spasm, nor did head trauma modify the age at onset of cranial dystonia. CONCLUSIONS: These results do not support prior head trauma as a possible environmental factor modifying the risk of developing late-onset cranial dystonia. The lack of association may have pathogenetic and medical-forensic implications.

Age of Onset↗

PubMed2006

Pisa syndrome without neuroleptic exposure in a patient with Parkinson's disease: case report.

We report on a patient affected by Parkinson's disease who developed over a period of a few weeks a tonic deviation of her head, neck, and trunk fitting the typical description of Pisa syndrome (PS). This patient was under stable levodopa and pramipexole treatment and had never been exposed to any psychotropic or antiemetic drugs before or at the time she developed the postural abnormality. Because dopamine transporter imaging revealed bilateral and symmetrical reduction of striatal uptake, we suggest that PS is not primarily related to side differences in dopaminergic denervation or drug exposure.

Aged↗

PubMed2006

Frequency and phenotypes of LRRK2 G2019S mutation in Italian patients with Parkinson's disease.

To evaluate the frequency of the LRRK2 G2019S mutation in Italy, we tested 1,072 probands with Parkinson's disease (PD; 822 sporadic and 250 familial): 20 patients (1.9%) carried the G2019S mutation, 11 patients (1.3%) were sporadic, and 9 (4.3%) had a positive family history. Considering only probands with autosomal dominant inheritance, the G2019S frequency raises to 5.2%. All presented a typical phenotype with variable onset and shared the common ancestral haplotype. Mutation frequency raised from 1.2% in early onset PD to 4.0% in late onset PD.

Amino Acid Substitution↗

PubMed2006

Temporal discrimination of two passive movements in writer's cramp.

Although movement abnormalities are predominant symptoms of dystonia, patients also have alterations in temporal as well as spatial discrimination of cutaneous inputs. Here, we use a recently described method to test whether deficits also exist in temporal discrimination of proprioceptive inputs. Percutaneous electrical stimulation of the motor point of the first dorsal interosseous (FDI) muscle, and of the flexor carpii radialis (FCR) muscle separately, was used to produce a nonpainful contraction of the muscles that caused index finger abduction and wrist flexion, respectively. In 10 patients with writer's cramp and in 10 healthy subjects, pairs of stimuli separated by different time intervals were given and subjects were asked to report whether they perceived a single or a double index finger abduction movement or wrist flexion. The threshold value was the shortest interval at which the subjects reported two separated movements (temporal discrimination motor threshold [TDMT]). In both writer's cramp patients and controls, TDMTs were higher for FCR than for FDI. But in contrast to the reduced temporal discrimination reported for cutaneous sensation, there was no significant difference in either muscle between TDMT in patients and normal subjects. We conclude that temporal processing of muscle and cutaneous afferents is differentially affected in focal hand dystonia.

Adult↗

PubMed2006

Atypical phenotypes and clinical variability in a large Italian family with DYT1-primary torsion dystonia.

The GAG deletion in the DYT1 gene usually causes a typical form of primary torsion dystonia (PTD) with early onset in a limb, rapid generalization, and sparing of cranial-cervical muscles, but atypical phenotypes have often been reported. Here, we describe a large DYT1 Italian family with phenotypically heterogeneous PTD that recapitulates all the atypical features associated with the DYT1 mutation, including late age at onset, focal or segmental phenotypes, onset or spreading of dystonia to the cranial-cervical muscles. Of 38 healthy family members, 15 also carried the DYT1 mutation, with an estimated penetrance of 21%. A literature review of atypical familial cases of DYT1-PTD showed that late onset, cervical involvement, and limited progression of dystonia are features frequently seen in DYT1 families. However, nearly all of these atypical patients fall within at least one of the clinical categories that best predict the DYT1 carrier status, namely, early onset, onset in a limb, and family history positive for early-onset dystonia.

Adult↗

PubMed2006

Effects of transcutaneous electrical nerve stimulation on motor cortex excitability in writer's cramp: neurophysiological and clinical correlations.

We recently reported that transcutaneous electrical nerve stimulation (TENS) applied over forearm flexor muscles, a paradigm producing in physiological conditions transient changes in corticomotoneuronal excitability of forearm muscles, may improve motor symptoms in writer's cramp (WC). In the present study, we explored the possibility that one or repeated sessions of TENS might have beneficial effects on handwriting in WC by remodulating cortical excitability of forearm agonist and antagonist muscles. Motor evoked potentials (MEPs) after transcranial magnetic stimulation of the left motor cortex were recorded from the right flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles, before and after 1 and 15 sessions of TENS applied over flexor muscles in patients and in a control group. One session of TENS induced a significant smaller reduction of MEPs from the FCR and a smaller increase of the MEPs from the ECR in patients than in normal subjects. In WC, repeated sessions of TENS had the effect to decrease MEP amplitude in the FCR and to increase it in the ECR. This modulation was paralleled by a handwriting improvement. In conclusion, repeated TENS sessions may have the effect to re-modulate excitability of the motor cortex in WC and this modulation might partially play a role in temporarily improving the handwriting.

Adult↗

PubMed2006

Comprehensive analysis of the LRRK2 gene in sixty families with Parkinson's disease.

Mutations in the gene leucine-rich repeat kinase 2 (LRRK2) have been recently identified in families with Parkinson's disease (PD). However, the prevalence and nature of LRRK2 mutations, the polymorphism content of the gene, and the associated phenotypes remain poorly understood. We performed a comprehensive study of this gene in a large sample of families with Parkinson's disease compatible with autosomal dominant inheritance (ADPD). The full-length open reading frame and splice sites of the LRRK2 gene (51 exons) were studied by genomic sequencing in 60 probands with ADPD (83% Italian). Pathogenic mutations were identified in six probands (10%): the heterozygous p.G2019S mutation in four (6.6%), and the heterozygous p.R1441C mutation in two (3.4%) probands. A further proband carried the heterozygous p.I1371 V mutation, for which a pathogenic role could not be established with certainty. In total, 13 novel disease-unrelated variants and three intronic changes of uncertain significance were also characterized. The phenotype associated with LRRK2 pathogenic mutations is the one of typical PD, but with a broad range of onset ages (mean 55.2, range 38-68 years) and, in some cases, slow disease progression. On the basis of the comprehensive study in a large sample, we conclude that pathogenic LRRK2 mutations are frequent in ADPD, and they cluster in the C-terminal half of the encoded protein. These data have implications both for understanding the molecular mechanisms of PD, and for directing the genetic screening in clinical practice.

Adult↗

PubMed2005

Selective impairment of hand mental rotation in patients with focal hand dystonia.

Mental rotation of body parts determines activation of cortical and subcortical systems involved in motor planning and execution, such as motor and premotor areas and basal ganglia. These structures are severely impaired in several movement disorders, including dystonia. Writer's cramp is the most common form of focal hand dystonia. This study investigates whether patients affected by writer's cramp present with difficulties in tasks involving mental rotation of body parts and whether any impairments are specific to the affected hand or generalized to other body parts. For this purpose we tested 15 patients with right writer's cramp (aged 21-68 years, 8 women) and 15 healthy control subjects (10 women, age and education matched). Stimuli consisted of realistic photographs of hands and feet presented on a computer monitor in different orientations with respect to the upright canonical orientation. In each trial, subjects gave a laterality judgement by reporting verbally whether the presented body part was left or right. Two main results of the study are, firstly, writer's cramp patients are slower than controls in mentally rotating hands [F (1,28) = 5.4; P = 0.028] but not feet, and secondly, the pattern of response times to stimuli at various orientations suggests that the mental motor imagery of controls and patients reflects the type of processes and mechanisms called into play during actual execution of the same movements. In particular, increased difficulty in rotating right-sided stimuli at 120 degrees and left-sided stimuli at 240 degrees would suggest that mental rotation of body parts reflects the anatomical constraints of real hand movements. In conclusion, patients with writer's cramp presented mental rotation deficits specific to the hand. Importantly, deficits were present during mental rotation of both the right (affected) and the left (unaffected) hand, thus suggesting that the observed alterations may be independent and even exist prior to overt manifestations of dystonia.

Adult↗

PubMed2005

Palatal tremor suppressed by mouth opening: clinical and neurophysiological correlations in two patients.

We report clinical and neurophysiological findings in two patients with palatal tremor (PT). In both patients a prompt and persistent suppression of palatal movements and clicking sounds is caused by slight passive or active mouth opening. One patient has a typical essential palatal tremor (EPT) according to current classification criteria. The other one has a PT characterized by involuntary activation of levator veli palatini and genioglossus muscles. Objective clicking sounds were observed late during the course of the disease. A symptomatic aetiology was excluded, suggesting a diagnosis of atypical EPT. Our observations further confirm that unusual features of some cases may not fit current PT classification criteria. These two cases have several features that distinguish them from voluntary PT and from psychogenic PT. We emphasize that clear cut modulating phenomena may be relevant features in both typical and atypical involuntary EPT. We finally focus on the significance of jaw posture in determining PT suppression in our patients.

Adult↗

PubMed2005

Temporal discrimination of two passive movements in humans: a new psychophysical approach to assessing kinaesthesia.

Percutaneous electrical stimulation of the motor point of the first dorsal interosseous muscle (FDI) was used to produce a non-painful contraction of the FDI muscle that caused index finger abduction movement but no radiating cutaneous paraesthesias or sharp sensations localized to joints. Pairs of stimuli separated by different time intervals were given and subjects were asked to report whether they perceived a single or a double index finger abduction movement. The threshold value was the shortest interval for which the subjects reported two separate index finger abduction movements. Temporal discrimination movement thresholds (TDMT) were measured for both right and left hand. To assess the possible role of muscle and cutaneous afferents in temporal discrimination, we investigated the effects of high-frequency (20 Hz) electrical stimulation of the right ulnar and radial nerves on TDMT. In humans, muscle afferents from FDI are supplied by the ulnar nerve whereas the cutaneous territory overlying the muscle and joint is supplied by the radial and median nerves. Threshold values were not significantly different for right (75.1 ms) and left (75.6 ms) hands. During ulnar and to a lesser extent during radial nerve stimulation, TDMT values were significantly increased (119.2 and 93.5 ms, respectively) compared with baseline conditions (78.0 ms) whereas no changes were observed during median nerve stimulation (80.5 ms). These results suggest that muscle, and in part cutaneous, afferents contribute to temporal discrimination of a dual movement. The technique may provide a useful way of measuring temporal discrimination of kinaesthetic inputs in humans.

Adult↗

PubMed2005

Task-specific impairment of motor cortical excitation and inhibition in patients with writer's cramp.

Abnormalities in motor cortical excitation and inhibition have been reported in patients with writer's cramp, at rest and during muscle activation. We were interested in whether such abnormalities might be task-specific and depended on the type of movement task used to activate the dystonic hand. We therefore assessed motor-evoked potentials (facilitation/rest MEP amplitude ratio) and duration of the cortical silent period (CSP) from the right first dorsal interosseus (FDI) muscle to transcranial magnetic stimulation (TMS) in 10 patients with writer's cramp and in 10 healthy volunteers performing pincer and power gripping tasks. The mean facilitation/rest MEP amplitude ratio measured during the pincer grip task was significantly larger in dystonic subjects than in controls, but in the power grip condition was similar in the two groups. The CSP measured in the power grip condition was of similar length in normal controls and dystonic subjects, but in the pincer grip condition was significantly shorter in patients than in controls. These results indicate a task-specific impairment of motor cortical excitation and inhibition in writer's cramp.

Adult↗

PubMed2005

Relationship between eye symptoms and blepharospasm: a multicenter case-control study.

Although patients with primary blepharospasm (BSP) commonly report experiencing ocular symptoms before the onset of orbicular spasms, the precise frequency and pathogenic role of this subjective ocular discomfort are poorly understood. We conducted a multicenter case-control study to investigate symptoms related to disorders of the anterior segment of the eye, administering a questionnaire to 165 patients with BSP and 180 age- and gender-matched control patients with hemifacial spasm. On a validation sample, our questionnaire yielded high accuracy in detecting eye diseases (predominantly, dry eye syndrome) using detailed ophthalmological examination as the criterion. Logistic regression analysis indicated a significant association between ocular symptoms at disease onset and BSP. Ocular symptoms starting in the year preceding disease onset (short-latency symptoms) showed a stronger association with BSP than ocular symptoms occurring earlier in time (long-latency symptoms). The association was stronger when short-latency symptoms developed from 40 to 59 years of age, whereas this was not observed for long-latency symptoms. Our findings support the view that eye symptoms associated with BSP result from eye diseases and may be involved in the pathogenesis of BSP. The differential risk of developing BSP, based on age at onset of ocular symptoms, suggests that age and eye diseases may interact in giving rise to BSP.

Age of Onset↗

PubMed2005

Inhibitory effect of capsaicin evoked trigeminal pain on warmth sensation and warmth evoked potentials.

The aim of the study was to evaluate the effect of tonic pain evoked by topical application of capsaicin on the somatosensory sensation of warmth. The warmth pathways were studied in ten healthy subjects by recording the scalp potentials evoked by non-painful warm laser stimuli delivered on both the right and left perioral region (warmth C-fiber related laser-evoked potentials (C-LEPs)). Tonic pain was induced by topical capsaicin application above the lateral part of the right upper lip. The area of primary and secondary hyperalgesia were mapped. C-LEPs were obtained from 31 scalp electrodes before, during, and after capsaicin application. C-LEPs from the right perioral region were evoked by laser stimuli delivered to the area of secondary hyperalgesia during capsaicin application and on both the areas of primary and secondary hyperalgesia after capsaicin removal. While the lateralized N1/P1 component (around 185 ms of latency) was not affected by the capsaicin, the amplitudes of the later vertex C-LEPs (around 260 and 410 ms of latency for the N2a and P2 potentials, respectively) evoked from the secondary hyperalgesic area on the right side and from a symmetrical non-hyperalgesic area on the left perioral region were significantly decreased during capsaicin application and after capsaicin removal, as compared with the baseline recordings. At the same times, the rating of the laser-evoked warmth sensation was reduced significantly. This inhibitory effect can occur at brainstem level and is possibly due to: 1) trigemino-cortico-trigeminal circuits, similar to those mediating the classical diffuse noxious inhibitory control, or 2) an increased background activity of the capsaicin-insensitive A-fibers, which mediate the secondary hyperalgesia. Probably due to a peripheral inhibitory mechanism, neither reliable C-LEP components nor warmth sensation were evoked by laser pulses delivered to the primary hyperalgesic area. This is the first neurophysiological evidence in humans of an inhibitory effect of pain on warmth sensation.

Adult↗

PubMed2004

Long-lasting modulation of human motor cortex following prolonged transcutaneous electrical nerve stimulation (TENS) of forearm muscles: evidence of reciprocal inhibition and facilitation.

Several lines of evidence indicate that motor cortex excitability can be modulated by manipulation of afferent inputs, like peripheral electrical stimulation. Most studies in humans mainly dealt with the effects of prolonged low-frequency peripheral nerve stimulation on motor cortical excitability, despite its being known from animal studies that high-frequency stimulation can also result in changes of the cortical excitability. To investigate the possible effects of high-frequency peripheral stimulation on motor cortical excitability we recorded motor-evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) of the left motor cortex from the right flexor carpi radialis (FCR), extensor carpi radialis (ECR), and first dorsal interosseous (FDI) in normal subjects, before and after transcutaneous electrical nerve stimulation (TENS) of 30 min duration applied over the FCR. The amplitude of MEPs from the FRC was significantly reduced from 10 to 35 min after TENS while the amplitude of MEPs from ECR was increased. No effects were observed in the FDI muscle. Indices of peripheral nerve (M-wave) and spinal cord excitability (H waves) did not change throughout the experiment. Electrical stimulation of the lateral antebrachial cutaneous nerve has no significant effect on motor cortex excitability. These findings suggest that TENS of forearm muscles can induce transient reciprocal inhibitory and facilitatory changes in corticomotoneuronal excitability of forearm flexor and extensor muscles lasting several minutes. These changes probably may occur at cortical site and seem to be mainly dependent on stimulation of muscle afferents. These findings might eventually lead to practical applications in rehabilitation, especially in those syndromes in which the excitatory and inhibitory balance between agonist and antagonist is severely impaired, such as spasticity and dystonia.

Adult↗

PubMed2004

Timing of tactile and visuo-tactile events is impaired in patients with cervical dystonia.

Psychophysical studies show alterations of cross-modal integration and timing processes in patients with generalized and focal hand dystonia. Here we assess the capability of 10 cervical dystonia patients, 5 patients with cervical pain but no dystonia, and 10 healthy controls to determine whether pairs of visual, tactile or visuo-tactile stimuli were simultaneous or sequential (TD threshold) and which stimulus preceded the other (temporal order judgement, TOJ). Visual stimuli consisted of light emitting diodes and tactile stimuli of non-noxious electrical shocks delivered to the hands. Intervals between stimuli were increased from 0 to 400 ms in steps of 10 ms. Cervical dystonia patients had a clear impairment of tactile and visuo-tactile temporal discrimination compared with patients with cervical pain but no dystonia who performed as well as healthy subjects. This suggests that deficits of temporal discrimination in cervical dystonia patients are not due to the possible distracting effect of unpleasant sensations or pain. Comparisons with previous studies show that deficits in cervical dystonia were more severe than in focal hand dystonia and less severe than in generalized dystonia. Thus, impairment of sensory timing may be a marker of disease, which varies along a continuum in the different forms of dystonia.

Adult↗

PubMed2003

Task-dependent modulation of excitatory and inhibitory functions within the human primary motor cortex.

We evaluated motor evoked potentials (MEPs) and duration of the cortical silent period (CSP) from the right first dorsal interosseous (FDI) muscle to transcranial magnetic stimulation (TMS) of the left motor cortex in ten healthy subjects performing different manual tasks. They abducted the index finger alone, pressed a strain gauge with the thumb and index finger in a pincer grip, and squeezed a 4-cm brass cylinder with all digits in a power grip. The level of FDI EMG activity across tasks was kept constant by providing subjects with acoustic-visual feedback of their muscle activity. The TMS elicited larger amplitude FDI MEPs during pincer and power grip than during the index finger abduction task, and larger amplitude MEPs during pincer gripping than during power gripping. The CSP was shorter during pincer and power grip than during the index finger abduction task and shorter during power gripping than during pincer gripping. These results suggest excitatory and inhibitory task-dependent changes in the motor cortex. Complex manual tasks (pincer and power gripping) elicit greater motor cortical excitation than a simple task (index finger abduction) presumably because they activate multiple synergistic muscles thus facilitating corticomotoneurons. The finger abduction task probably yielded greater motor cortical inhibition than the pincer and power tasks because muscles uninvolved in the task activated the cortical inhibitory circuit. Increased cortical excitatory and inhibitory functions during precision tasks (pincer gripping) probably explain why MEPs have larger amplitudes and CSPs have longer durations during pincer gripping than during power gripping.

Adult↗