Natalizumab treatment in multiple sclerosis patients: a multicenter experience in clinical practice in Italy.

We evaluated efficacy of natalizumab in relapsing-remitting multiple sclerosis patients in a clinical practice setting. We report data on the first consecutive 343 patients receiving natalizumab in 12 multiple sclerosis (MS) Italian centers enrolled between April 2007 and November 2010. The main efficacy endpoints were the proportion of patients free from relapses, disease progression, combined clinical activity, defined as presence of relapse or disease progression, from MRI activity, and from any disease activity defined as the absence of any single or combined activity. At the end of follow-up, the cumulative proportion of patients free from relapses was 68%; the proportion of patients free from Expanded Disability Status Scale (EDSS) progression was 93%; the proportion of patients free from combined clinical activity was 65%; the proportion of patients free from MRI activity was 77%; and the proportion of patients free from any disease activity was 53%. Natalizumab was effective in reducing clinical and neuroradiological disease activity. Its effectiveness in clinical practice is higher than that reported in pivotal trials and was maintained over time.

Post-traumatic headaches: a clinical overview.

Headache attributed to head and/or neck trauma or injury, the so-called post-traumatic headache (PTH), is the most common secondary headache disorder and one of the most controversial clinical entities in the headache field, due to its unclear pathophysiological mechanisms and the unsolved role of associated psychological and medico-legal aspects. PTH, as a significant cause of morbidity after traumatic brain injury, may occur as an isolated symptom or as one of a constellation of symptoms known as post-concussive syndrome. However, in many cases, PTH might also represent an accentuation of non-disabling, remote or infrequent pre-existing primary headaches rather than a new onset headache strictly related to the trauma. Recently, the International Classification of Headache Disorders attempted to classify PTH; however, many unsolved issues are still to be clarified. In this brief review, we will focus on PTH clinical aspects and diagnostic criteria.

Basilar-type migraine patients responsive to lamotrigine: a 5-year follow-up.

Five years ago we reported the case of three patients affected by basilar-type migraine (BM) responsive to lamotrigine. At that time, proven treatment options for BM are rather limited and lamotrigine has been tested in BM patients because it was a widely tested treatment for migraine with aura. That positive 1-year experience leaded us to suggest that lamotrigine could be a preventive therapeutic option for BM patients, with and without menstruation association. We now report the five-year follow-up of the same patients to confirm and underlie the possible role of lamotrigine to induce BM attacks remission.

Triptans: over the migraine.

Migraine is a chronic, recurrent, disabling condition that affects millions of people worldwide. Proper acute care treatment for migraineurs is based on triptans, a class of specific medications approved over 20 years ago. Triptans are serotonin (5-HT1B/1D) receptor agonists that are generally effective, well tolerated and safe. Seven triptans are available worldwide, although not all are available in every country, with multiple routes of administration, giving to doctors and patients a wide choice. Despite the similarities of the available triptans, pharmacological heterogeneity offers slightly different efficacy profiles. Triptans are not pain medications, they are abortive migraine medications which cannot prevent migraines. In addition to migraine attacks, triptans are also helpful for cluster headaches. If they are useful in other primary headaches rather than migraine and cluster headache it is yet to be addressed. In the literature there are only limited controlled clinical data to support a migraine-selective activity for triptans. Reports are available about efficacy of triptans to stop attacks of other types of primary headache, such as tension type headache, hypnic headache and other rare forms of primary headaches. On the other hand, sumatriptan failed to treat the indomethacin-responsive primary headache disorders like chronic paroxysmal hemicrania and hemicrania continua, nor was it effective in the myofascial temporal muscle pain or in atypical facial pain. Why triptans are effective in so different types of primary headaches remain unclear. Up to date, it is not clear whether the antimigrainous activity of the triptans involves an action only in the periphery or in the CNS as well. Probably we should consider triptans as "pain killers" and not only as "migraine killers". We clearly need additional studies on triptans as putative analgesics in well-accepted animal and clinical models of acute and chronic somatic pain.

Migraine and movement disorders.

A large series of clinical and experimental observations on the interactions between migraine and the extrapyramidal system are available. Some previous studies reported high frequency of migraine in some basal ganglia (BG) disorders, such as essential tremor (ET), Tourette's syndrome (TS), Sydenham's chorea and more recently restless legs syndrome (RLS). For example, the frequency of migraine headache in a clinic sample of TS patients was found nearly fourfold more than that reported in the general population. To the best of our knowledge, no controlled studies have been conducted to determine a real association. ET and migraine headache have been considered comorbid diseases on the basis of uncontrolled studies for many years. In a recent Italian study, this comorbid association has been excluded, reporting no significant differences in the frequency of lifetime and current migraine between patients with ET and controls. Among mostly common movement disorders, RLS has been recently considered as possibly comorbid with migraine. Studies in selected patient groups strongly suggest that RLS is more common in migraine patients than in control populations, although no population-based study of the coincidence of migraine and RLS has yet been identified. The exact mechanisms and contributing factors for a positive association between migraine and RLS remain unclear. A number of possible explanations have been offered for the association of RLS and primary headache, but the three most attractive ones are a hypothetical dopaminergic dysfunction and dysfunctional brain iron metabolism, a possible genetic linkage and a sleep disturbance. More recently, the role of BG in pain processing has been confirmed by functional imaging data in the caudate, putamen and pallidum in migraine patients. A critical appraisal of all these clinical and experimental data suggests that the extrapyramidal system is somehow related to migraine. Although the primary involvement of extrapyramidal system in the pathophysiology of migraine cannot as yet be proven, a more general role in the processing of nociceptive information and/or maybe part of the complex behavioral adaptive response that characterizes migraine may be suggested.

Restless legs syndrome is not associated with migraine with aura: a clinical study.

Based on recent data about the association between restless legs syndrome (RLS) and migraine, we performed an observational study on the occurrence of RLS in patients affected by "pure" migraine with aura (pMA). We recruited 63 patients (33 females and 30 males) affected by MA without other types of primary headache among all patients referred in five Italian headache centers in a 1-year period. The prevalence of RLS in pMA patients (9.5%) is similar to that observed in Italian headache-free subjects (8.3%). No significant differences were found between pMA patients with and without RLS about clinical features of MA attacks and systemic and psychiatric diseases were investigated. Moreover, no association appeared between RLS and familial cases of MA. Differently from migraine without aura, our data do not confirm the existence of an association between RLS and MA, not even when a genetic factor is involved.

Apathy in Parkinson's disease: differences between caregiver's report and self-evaluation.

Apathy is a state of diminished goal-directed speech, motor activity and emotions. The prevalence of apathy in Parkinson's disease (PD) ranges from 16 to 62%. Several studies have investigated the relationships between apathy and other dimensions of PD, but little is known about possible discrepancies between self-evaluation (SE) and caregiver reporting (CR) of this symptom. The aim of this study is twofold: 1) to investigate the differences in apathy evaluations according to the point of view from which apathy is reported (SE vs CR); 2) to identify the possible relationships between each of the two evaluations (SE and CR) and cognitive and affective dimensions of PD. Forty-eight patients with PD were assessed using the Apathy Evaluation Scale (AES) in its SE and CR versions (AES-SE and AES-CR); cognitive, affective and behavioral symptoms were also assessed. AES-SE scores were significantly higher than AESCR ones. Neither AES version correlated with depression, whereas both correlated with motor impairment, disease stage and behavioral symptoms. Mini-Mental State Examination and Frontal Assessment Battery scores showed significant negative correlations only with AES-SE scores. Our findings suggest that the point of view from which apathy is seen can lead to significant discrepancies, even when using the same tool. This should be taken into account in order to obtain correct assessment of this disabling and distressing symptom.

Mutation of dystrophin gene and cardiomyopathy.

The correlations between the type of gene mutation and the cardiac clinical picture were examined in 284 patients with dystrophinopathy (200 Duchenne and 84 Becker). The subjects with normal heart showed deletions including exons 48-49 in 21.4% DMD and in 25% BMD, and other deletions in 35.7% DMD and 25% BMD; vice versa the cases with severe cardiac involvement showed deletions including 48-49 in 38.8% DMD and 37.5% BMD and other deletions in 32.9% DMD and 20% BMD. The age of death was 18 years in DMD patients with deletions including 48-49 whereas the age was about 22 in the cases with other deletions. The differences were statistically significant.

Evaluation of cardiac and respiratory involvement in sarcoglycanopathies.

Sarcoglycanopathies constitute a subgroup of limb-girdle recessive muscular dystrophies due to defects in sarcoglycan complex that comprises five distinct transmembrane proteins called alpha-, beta-, gamma-, delta-and epsilon-sarcoglycans. As it is well known that sarcoglycans are expressed both in heart and in skeletal muscles and a complete deficiency in delta-sarcoglycan is the cause of the Syrian hamster BIO.14 cardiomyopathy, we studied cardiac and respiratory involvement in 20 patients with sarcoglycanopathies by clinical, electrocardiographic, echocardiographic, scintigraphic and spirometric assessments. A normal heart function was found in 31.3% of all patients; a preclinical cardiomyopathy in 43.7%; an arrhythmogenic cardiomyopathy in 6.3% and initial signs of dilated cardiomyopathy in 18.7%. In one patient the data were examined retrospectively. No correlation was found between cardiac and skeletal muscle involvement. With reference to the type of sarcoglycanopathy, signs of hypoxic myocardial damage occurred in beta-, gamma- and delta-sarcoglycanopathies, while initial signs of a dilated cardiomyopathy in gamma- and delta-sarcoglycanopathies were found. A normal respiratory function was observed in 23.5% of all patients, a mild impairment in 35.4%, a moderate impairment in 29.4%, and a severe impairment in 11.7%.

Left ventricular function and perfusion in Becker's muscular dystrophy.

UNLABELLED: The aim of this study was to evaluate left ventricular (LV) perfusion and function in patients with Becker muscular dystrophy (BMD). METHODS: Fourteen male patients (age range 14-40 yr) with BMD were evaluated by 201Tl SPECT and radionuclide angiography both at rest and after dipyridamole stress test. RESULTS: All patients showed uptake defect demonstrated by 201Tl SPECT (mean 4.1 +/- 2.2 uptake defect/patient). Significant relationships (p < 0.05) were found between the number of uptake defects and rest LV ejection fraction (LVEF) (r = -0.54); peak filling rate (PFR) (r = -0.57) and dipyridamole LVEF (r = -0.65). Dipyridamole induced reversible uptake defects were found in 7/14 (50%) patients with BMD. The 14 patients were divided into two groups on the basis of the presence (Group A, n = 6) or the absence (Group B, n = 8) of severe irreversible uptake defect (i.e., < 50% 201Tl uptake). Group A showed lower values of PFR and LVEF when compared to patients of Group B. CONCLUSIONS: In patients with BMD there is a relatively high incidence of uptake defects and LV function (both at rest and after dipyridamole) appears to be related to the number of uptake defects. Moreover, the presence of severe irreversible uptake defects identifies a subgroup of patients with BMD characterized by a severely depressed LV function.

Multisystem involvement of the central nervous system in Strümpell's disease. A neurophysiological and neuropsychological study.

The multisystem involvement of the central nervous system (CNS) in familial spastic paraplegia (FSP) has not been fully investigated by means of complete neurophysiological and neuropsychological examinations. The classification which distinguishes pure and complicated forms of FSP, is based on clinical features and does not take into account the possibility that clinically silent lesions of the CNS can be identified by means of adequate tests. The study was intended to assess the subclinical and multisystem involvement of the CNS in a group of 11 patients affected by FSP, clinically distinguished in 7 pure forms and 4 complicated forms. Neurophysiological tests included saccadic eye movements analysis, visual and auditory brain stem evoked responses. Neuropsychological examination was devised by means of a special purpose mental deterioration battery. Our results, showing a high incidence of multisystemic subclinical involvement of the CNS, confirm and extend the concept that FSP is a multisystemic degenerative disease of the CNS, and that the existence of "pure" forms should be reconsidered.

The cardiomyopathy of Duchenne/Becker consultands.

Clinical, electrocardiographic, echocardiographic and other instrumental examinations were performed on 233 persons primarily seeking genetic advice about the Duchenne/Becker gene in order to reveal the incidence of dystrophic cardiomyopathy in a population of females with a close relationship with patients suffering from Duchenne or Becker muscular dystrophy. Among these consultands, 210 were Duchenne and 23 Becker. Eight five (40.4%) Duchenne and 8 (34.8%) Becker consultands showed a normal cardiac status; 35 (16.6%) Duchenne and 6 (26.1%) Becker had clinically evident cardiomyopathy; 90 (43%) Duchenne and 9 (39.1%) Becker showed minor signs of myocardial involvement. The link between myocardial involvement and the Duchenne/Becker carrier condition was demonstrated through the observation that the percentage of cases showing pre-clinical or clinically evident cardiomyopathy was higher in the consultands with pathological values of serum creatine kinase activity (obligatory carriers) and/or an estimated genetic risk higher than 70% than in the consultands showing a normal value of serum creatine kinase activity (less than 80 U/l) and/or a genetic risk lower than 70%.

Autonomic nervous system imbalance and left ventricular systolic dysfunction as potential candidates for arrhythmogenesis in Becker muscular dystrophy.

We evaluated the arrhythmic profile in a population of 20 Becker muscular dystrophy (BMD) patients searching for possible correlations between the severity of the arrhythmic events, the cardiac autonomic balance (assessed by heart rate variability analysis in the time domain) and the degree of left ventricular systolic impairment. A population of 14 male healthy individuals served as the control group. BMD subjects exhibited lower values of SDNN (P=0.013), SDANN index (P=0.008) and 24-h mean heart rate (P=0.002). The total number of premature ventricular beats (totPVB) and the number of PVB out of 1000 heartbeats (PVB/1000) appeared also higher in BMD subjects (P=0.05 and P=0.046, respectively). No difference was found in terms of 24-h mean QTc and 24-h longest QT among the two groups. TotPVB and PVB/1000 were inversely related to both the ejection fraction (r= -0.620, P=0.004 and r= -0.517, P=0.019) and to the shortening fraction (r= -0.568, P=0.009 and r= -0.469, P=0.037). Twenty-four-h mean QTc was also inversely related to both the ejection fraction (r= -0.520, P=0.019) and the fractional shortening (r= -0.491, P=0.028). These data suggest that in BMD there is cardiac autonomic imbalance characterized by sympathetic predominance and an increased susceptibility to ventricular arrhythmias, even in the absence of overt cardiomyopathy. Furthermore, the severity of the arrhythmic profile in BMD appears closely related to the degree of left ventricular systolic dysfunction.

Cardiomyopathies: diagnosis of types and stages.

Primary cardiomyopathies have as dominant feature the involvement of heart muscle itself. They are not the result of other diseases and should be defined as diseases of heart muscle not consequent to disorders of other parts of the cardiovascular apparatus. Most of them are consequent to genetic defects and can be subdivided into three major groups: isolated, associated with skeletal muscle diseases, associated with neurological disorders. Primary cardiomyopathies show an evolution from mild to more severe stages. Four types of cardiomyopathies are classically described: dilated, hypertrophic, restrictive and arrhythmogenic. However, from a clinical point of view, it is possible to distinguish seven stages: pre-clinical, prevalently arrhythmogenic, prevalently pseudo-hypertrophic, spotty fibrotic, restrictive, dilated and refractory heart failure. In the course of their evolution, cardiomyopathies can shift from a clinical picture to another, consequently requiring frequent examinations of patients in order to adjust their treatment.

ST-segment displacement in Duchenne muscular dystrophy: myocardial necrosis or apoptosis?

An electrocardiographic pattern resembling myocardial infarction is a rare condition in Duchenne muscular dystrophy. We report the case of a Duchenne boy, aged 12 years and 7 month, who, during a programmed examination, showed electrocardiographic signs of ST segment elevation, without symptoms usually accompanying myocardial infarction (chest pain, dyspnoea, sweating). The biological markers of myocardial damage became positive on the 2nd day and recovered on the 5th day. Clinical features of this uncommon pattern are described, with the retrospective evaluation of similar cases from personal records. The differential diagnosis between myocardial necrosis and apoptosis is discussed.

[Specific and aspecific myocardial changes in progressive muscular dystrophy and their importance in rehabilitative treatment]. / Alterazioni miocardiche specifiche ed aspecifiche nel quadro delle miodistrofie progressive e loro importanza nella terapia riabilitativa.

Clinical and instrumental parameters studied in over 200 progressive muscular dystrophy patients during a period of about 10 yr revealed four different types of cardiopathy in this disease. The most interesting finding was that 38% of patients with Duchènne's dystrophy presented a clinical and ECG picture reminiscent of that of obstructive hypertrophic cardiomyopathy. Some suggestions are made for the pharmacological and rehabilitative management of subjects with myocardiopathy in the course of myodystrophy.

Frovatriptan for the prevention of postdural puncture headache.

Efficacy of 5-day treatment with oral frovatriptan 2.5 mg/die for the prophylaxis of post-dural puncture headache (PDPH) was tested in 50 in-patients. A mild headache occurred in 7 (14%) patients for a total of 9 days (p < 0.01 vs. no-PDPH). Most episodes of PDPH occurred in the first days of treatment (only 1 patient had headache at dismissal): 5 patients had only 1 episode, while 2 had headache for 2 consecutive days. No other symptoms were recorded. Occurrence of PDPH in a subgroup of 6 (12%) patients previously submitted to a diagnostic lumbar puncture was also examined: 4 of them reported a PDPH on the previous lumbar puncture in absence of triptans. In only 1 of these 4 patients PDPH recurred under treatment with frovatriptan. In conclusion, our non-randomized open-label study suggests efficacy of oral frovatriptan for PDPH prevention. These results need to be confirmed in a randomized, controlled, double-blind study.

Basilar-type migraine responsive to lamotrigine: three case reports.

Basilar-type migraine (BM) has been recognised in the revised International Classification of Headache Disorders as a distinct clinical entity (subtype of migraine with aura), characterised by disturbing migraine aura clearly originating from the brainstem or from both hemispheres simultaneously affected. It differs from familial and sporadic hemiplegic migraines by the absence of motor deficit. Lamotrigine has been shown to be effective in preventing migraine aura symptoms in typical aura and in some cases of BM. We tried lamotrigine in three female cases of BM.