Morena Giovannelli

Impairment of individual finger movements in Parkinson's disease

By analyzing the kinematics of repetitive, constant‐amplitude, finger oppositions, we compared the impairment of individual and nonindividual finger movements in patients with Parkinsons disease. In one task, subjects tapped only the index finger against the thumb (individual oppositions); in the other task, they tapped all four fingers together against the thumb pad (nonindividual oppositions). We used an optoelectronic motion analysis system to record movements in three‐dimensional space and recorded three 5‐second trials for each task. We counted how many finger oppositions subjects performed during each trial and measured the duration and amplitude of the flexions and extensions. We also calculated the duration of the pauses after flexion and extension. We assessed the deterioration of motor performance in patients by investigating the changes in speed and amplitude with task completion. During both tasks, normal subjects and patients performed finger flexions faster than extensions, and they invariably paused longer after flexion than after extension. Patients performed individual and nonindividual finger movements slowly and with reduced amplitude. Patients were disproportionately slow during flexion and in switching from flexion to extension. Movement slowness increased as finger oppositions progressed but predominantly when patients had to move fingers individually. In conclusion, in patients with Parkinsons disease, the motor performance deteriorated with task completion more during individual than during nonindividual finger movements. Parkinsons disease, therefore, impairs individual finger movements more than gross hand movements. This distinction reflects the finer cortical control needed to promote and sustain this highly fractionated type of motor output.

Movement cueing and motor execution in patients with dystonia: A kinematic study

To investigate whether the type of movement cueing influences motor performance in patients with dystonia, we studied externally triggered (ET) and self‐initiated (SI) sequential rapid arm movements in patients with generalized or focal dystonia and healthy control subjects. The ET task required subjects to initiate movements in response to consecutive visual cues; the SI task allowed them to start at will. To determine whether patients found sequential motor tasks more difficult than single tasks, we also analyzed single ET movements. Control subjects performed the SI task significantly faster than the ET task. Their single ET movements and first ET sequential submovements had similar speeds. Patients with generalized dystonia were slow in performing the single movement, the ET and the SI sequential tasks, and they executed the SI sequence more slowly than the ET. They made long pauses between SI sequential submovements, had longer reaction times during the ET sequences, and performed the first ET submovement more slowly than the single ET movement. Patients with focal dystonia had normal reaction times but they performed single and sequential tasks slowly, made long pauses during SI tasks, and also executed the first ET submovement more slowly than the single ET movement. Our findings indicate that patients with dystonia have a general impairment of sequential movements. The more marked slowness in executing SI than ET movements observed in patients with generalized dystonia shows that dystonia impairs internal cueing more than external cueing mechanisms. Overall, these findings imply abnormal activation of primary and nonprimary motor areas during movement in dystonia. The greater impairment of SI tasks as well as the delayed motor responses during ET task suggest predominant underactivity of the supplementary motor area.

The prolonged cortical silent period in patients with Huntington's disease

OBJECTIVES In a group of patients with Huntingtons disease and age-matched controls, we studied the cortical silent period (SP) elicited by single transcranial magnetic stimulation (TMS) pulses. METHODS We measured the area of the pre-stimulus electromyographic (EMG) activity, the area of the motor evoked potentials (MEPs) and the duration of the SP induced by stimuli delivered at an intensity of 150% of motor threshold with a round coil placed over the vertex. We determined the cortical SP by sampling only the 5 traces containing the shortest SPs and by collecting 10 consecutive unselected traces without selecting trials. RESULTS Patients and controls had normal EMG background areas, and MEP latencies and areas. Whereas data measured from selected trials gave a normal duration of the SP (patients, 154+/-58 ms; controls, 166+/-22 ms), data from unselected trials yielded a significantly longer SP duration in patients than in controls (356+/-251 vs. 159+/-44 ms) and also a larger variance and range. CONCLUSIONS We conclude that in Huntingtons disease, an abnormal cortical SP is best sought by collecting unselected consecutive traces. We suggest that the prolonged SP in HD originates from a dysfunction of the mechanisms controlling the restart of voluntary movement after TMS.

Cortical excitability in patients with essential tremor

We used transcranial magnetic stimulation in 10 patients with essential tremor and 8 matched healthy subjects. A round stimulating coil was placed over the vertex and electromyographic activity was recorded from the first dorsal interosseous muscle. Paired transcranial stimuli were delivered at interstimulus intervals of 3, 5, 20, 100, 150, and 200 ms. The intensity of the conditioning stimulus was 80% of motor threshold at short and 150% at long interstimulus intervals (ISIs). We also measured the silent period obtained after a single magnetic pulse delivered at 150% of motor threshold during a submaximal muscle contraction. Patients and controls had similar motor threshold and similar latencies. Paired magnetic stimuli given at short and long ISIs at rest, and during a voluntary muscle contraction, elicited similar responses in both groups. The silent period evoked by transcranial magnetic stimulation had a similar duration in patients with ET and controls. In conclusion, these findings suggest that patients with essential tremor have normal cortical motor area excitability.

Dopamine transporter immunoreactivity in peripheral blood lymphocytes discriminates Parkinson’s disease from essential tremor

SummaryPeripheral blood lymphocytes (PBL) provide a model to study the changes of neurotransmitter-receptor systems in neurodegenerative disorders, including Parkinson’s disease (PD). In this study, densitometric analysis was applied to measure dopamine transporter (DAT) immunoreactivity in PBL from dopaminergic drug-free patients suffering PD or essential tremor (ET) with respect to healthy subjects. The results showed a significant reduction of DAT immunoreactivity in PBL in PD but not in ET. These finding suggests that DAT immunoreactivity in PBL may discriminate between PD and ET in the early clinical stages.

Central and peripheral dopamine transporter reduction in Parkinson's disease

Abstract Objective: Previous reports showed the reduction of dopamine transporter immunoreactivity in peripheral blood lymphocytes in Parkinsons disease. In this work, we sought to investigate the possible correlation between central and peripheral dopamine transporter immunoreactivity values in a group of 11 drug-naive patients with Parkinsons disease. Methods: Densitometric measurements of dopamine transporter immunoreactivity in peripheral blood lymphocytes was accomplished as described recently, using a monoclonal antidopamine transporter antibody. Dopamine transporter binding in the caudate and putamen nuclei was measured by means of 123I-fluopane single-photon emission computed tomography in the same patients. Results: The results failed to show any significant correlation between dopamine transporter immunoreactivity in peripheral blood lymphocytes and the caudate or putamen dopamine transporter binding. Moreover, dopamine transporter immunoreactivity in peripheral blood lymphocytes was reduced also in the single patient with normal striatal dopamine transporter binding. Discussion: These results indicate the lack of correlation between central and peripheral dopamine transporter reduction in Parkinsons disease, using the methodologies applied herein. They therefore suggest that the two phenomena are unlikely to share a common pathogenetic mechanism.

Entacapone in elderly parkinsonian patients experiencing levodopa-related wearing-off: A pilot study

Abstract Levodopa (LD) provides the most effective symptomatic treatment for Parkinsons disease (PD). Long-term treatment with LD, however, is often associated with the development of response fluctuations. Previous evidence suggests that the short half-life of LD is a major contributor to the development of response fluctuations and the wearing-off phenomenon in particular. Entacapone, a peripheral catechol-O-methyltransferase inhibitor has been shown to reduce OFF time and increase ON time in several therapeutic trials on PD patients treated with LD experiencing motor fluctuations. However, data are missing on the tolerability and efficacy of entacapone in elderly PD patients. This is of particular relevance, as most PD patients develop LD-related motor fluctuations after several years of disease duration. Here we report that addition of entacapone in a group of 45 elderly PD patients with LD-related motor fluctuations is well tolerated and efficacious in reducing the time, frequency and severity of the OFF periods. These data suggest that the drug can be used safely and efficaciously in elderly PD patients.

Dopamine transporter immunoreactivity in peripheral blood lymphocytes in multiple system atrophy.

Previous studies showed the reduction of dopamine transporter immunoreactivity (DAT-IR) in peripheral blood lymphocytes (PBL) in Parkinson’s disease. Here we report the reduction of DAT-IR in PBL in the extrapyramidal variant of multiple system atrophy. These results suggest the reduction of DAT-IR in PBL in a variety of neurodegenerative disorders, provided the presence of damage of the central dopaminergic systems. The reduction of DAT-IR in PBL in these disorders may represent a compensatory phenomenon aimed at reducing intracellular dopamine influx and, consequently, dopamine-mediated aggravation of oxidative stress in these cells.

Fahr’s disease detected on a head CT scan in patient with “epileptic syncope” in the Emergency Department

Fahr’s disease is a rare neurological disorder characterized by diffuse intracranial calcification with a prevalent involvement of the basal ganglia and dentate nucleus of the cerebellum. It has been reported to be an autosomal dominant inheritance in familial cases, although the causal gene is still unknown, and sporadic types have been described. Most cases initially present with a deterioration of motor function. Later in the development of the disease, other symptoms and signs occur, especially extrapyramidal symptoms. We report a case with an unusual presentation and no extrapyramidal signs: An 58-year-old woman was brought to the Emergency Department (ED) because of a sudden loss of consciousness with seizure and urinary incontinence. She denied chest or abdominal pain, nausea vomiting or diarrhea. Upon falling from the seizure, she sustained cranial trauma (frontal skull). She denied any past medication history, allergies to medications, chest or abdominal pain, nausea, vomiting or diarrhea. There was no family history of mental illness, dementia, or major physical illness. Prior to the present illness, she had been living independently. On physical examination, the patient was a healthy appearing woman who was 155 cm tall, and weighed 49 kg. The vital signs were: blood pressure 140/85 mmHg, pulse 70 beats/min, respirations 12 breaths/min, temperature 37 C. The general physical examination other than the skull contusion was unremarkable. Neurological examination revealed cerebellar ataxia (antagonist hypotonia, asynergy, dismetria and dysdiadochokinesia); there were no extrapyramidal signs, athetosis or dementia; normal cranial nerve functions, and no motor or sensory focal findings. A laboratory screening panel was normal including calcium (8.9 mg/dL) and phosphate (3.1 mg/dL). Because of the new onset seizure activity, a non-contrast head computed tomography (CT scan) was obtained, and revealed extensive and symmetrical hyper-dense lesions over the caudate, dentate nuclei and periventricular white substance (Figs. 1, 2). The patient was admitted to the medicine ward, where other examinations were performed. Routine laboratory investigation confirmed that calcium and phosphate ions were in normal range; also normal were other tests including inflammation indices and coagulation tests. An electroencephalogram (EEG) revealed a normal pattern. Imaging diagnostic procedures gave no evidence of radiographic cardiopulmonary lesions, and there were no tumors of bone or other organs. Magnetic resonance imaging of the head revealed multiple areas of modified intensity signal, hyper-intense in T2, softly hyper-intense in T1 calibrated images and hypointense using the echo gradient technique, localized into peri-ventricular area, semi-oval centers, basal nuclei and cerebellum dentate nucleus. A. Sentimentale (&) M. Matteoli M. Corsino E. Ferri S. Di Somma Department of Emergency Medicine, II Medical School University La Sapienza, Sant’Andrea Hospital, Via di Grottarossa 1035-1039, 00189 Rome, Italy e-mail: alberto.sentimentale@ospedalesantandrea.it

Treatment with botulinum toxin for anti-MAG neuropathy-related arm tremor

Anti-MAG polyneuropathy is a peripheral neuropathy associated with monoclonal gammopathy, characterized by progressive, symmetric, mostly sensory impairment and mild distal muscle weakness, with limited response to immune therapies [1]. Gait ataxia and limb tremor with poor response to pharmacological treatment are prominent features [2]. Here we report the case of a female affected by anti-MAG polyneuropathy, who experienced significant improvement of upper limb tremor following repeated botulinum toxin injections. The patient presented with bilateral glove and stocking paresthesia at the age of 52, complicated within 10 months by distal muscle weakness, gait ataxia and bilateral arm tremor. She did not have family or personal history of tremor. The neurological examination showed postural and action tremor of the upper limbs, weakness of the distal muscles of the 4 limbs, areflexia, distal sensory deficit and gait ataxia. The electroneurographic examination revealed sensory-motor demyelinating polyneuropathy with associated neuronal damage at the lower limbs. CSF examination showed increased protein level, monoclonal gamma/IgM band and high titer of anti-MAG antibodies were detected in the serum. Over years, she experienced moderate improvement of sensory ataxia following treatment with corticosteroids, intravenous immunoglobulins, cyclophosphamide and rituximab. Tremor, however, worsened progressively and at the age of 65 was severe enough to impede writing, dressing, feeding and drinking. At that time, there was a slow, irregular, postural tremor of the hands, accentuated by goal-directed movement, with significant internalexternal rotatory component at the shoulders, flexor–extensor component at the elbows and slight flexor–extensor component at the wrists. Tremor did not respond to primidone, clonazepam, gabapentin, pregabalin and topiramate. Propanolol was not used because of bradycardia. Botulinum toxin (BT) is currently a second-line therapy for essential tremor [3] and tremors from other origins. Moreover, BT showed efficacy on proximal limb tremor from central nervous system diseases [4]. We hypothesized that BT might prove useful also for tremor in our patient. The procedure was approved by our Ethical Committee and the patient signed informed consent before treatment. Initially, we infiltrated BT into the deltoid and tricep bilaterally (Incobotulinumtoxin A 300 UI per arm). On the second and third treatment session, at 3-month interval each, tricep and bicep were bilaterally injected (400 UI total, 200 UI per arm). At all time points, muscles were selected based on the evidence of tremulous activity at palpation and at electromyography. Following the third injection of BT, the patient experienced a significant and long-lasting reduction of tremor severity and gained autonomy in drinking and feeding. Muscle strength was unaffected by BT injections and the patient did not report any side effect from treatment. At the last neurological evaluation, 5 months after the last injection, the patient has retained the benefits of BT. The mechanisms underlying tremor in anti-MAG polyneuropathy is incompletely defined. Bain et al. [2] P. Latino C. Pellicano F. E. Pontieri M. Giovannelli (&) UOC Neurologia, Azienda Ospedaliera ‘‘Sant’Andrea’’, Via di Grottarossa, 1035, 00189 Rome, Italy e-mail: giovannelli.morena@gmail.com