Diabetic Polyneuropathy and Physical Activity in Type 1 Diabetes Mellitus: A Cross-Sectional Study.

BACKGROUND: The purpose of this study is to access whether a personal attitude to physical activity (PA) may influence the appearance of diabetic polyneuropathy (DPN) patients with well-controlled type 1 diabetes mellitus. METHODS: Ninety patients attending the diabetes technology outpatient clinic were enrolled. DPN was investigated according to the Toronto consensus diagnostic criteria. PA was assessed using the International Physical Activity Questionnaire. RESULTS: PA was low in 21.1%, moderate in 42.2% and high in 36.7% of patients. According to Toronto criteria, we defined two categories: the first one with DPN absent or possible (57 (63.3%)) and a second one with DPN certain or probable (33 (36.7%)). The χ2-test of the PA groups and the DPN categories showed a statistically significant difference (p < 0.001), with less neuropathy in patients belonging to the group of moderate/high PA. Exposure to a minimum of 600 MET minutes/week was protective factor against the onset of DPN (odd ratio 0.221, c.i. 0.068-0.720, p = 0.012). CONCLUSIONS: This study suggests that DPN is less present in type 1 diabetic patients with good metabolic control and a good personal habit of PA. Moderate-to-vigorous PA of at least 600 MET minutes/week might be a protective factor against DPN.

Extended release levodopa at bedtime as a treatment for nocturiain Parkinson's disease: An open label study.

BACKGROUND: Bladder dysfunction may cause disabling symptoms in Parkinson's disease (PD) patients. The majority patients' experience symptoms as urinary urgency and nocturia suggest overactive bladder. This seems to be due to an altered brain-bladder relationship because of alteration in fronto-basal ganglia D1-dopaminergic circuit that normally suppresses micturition-reflex. Previous studies demonstrated beneficial effect of D1/D2 dopamine-receptors chronic-stimulation on detrusor overactivity of PD-patients.The present study was aimed to evaluate possible effect of extended-release (ER) Levodopa administered at bed-time on both nocturia and nocturia-related quality-of-life (NQoL) in PD-patients. METHODS: 106 PD-patients (Hoehn and Yahr>1 and < 4, mean age 66 years, 59 females and 47 males) were enrolled by 7 Movement Disorders out-patients clinics. Patients undergo to International Prostatic Symptoms Scale-IPSS, including 1-item about nocturia (item 7), and to Nocturia Quality of Life-NQoL questionnaire, at baseline and after two-months of Extended-Release L-dopa (L-dopa/carbidopa or L-dopa benserazide) treatment at bed-time. RESULTS: Statistical analysis showed significant improvement on both total IPSS, item 7and NQoL scores following two-months ER L-dopa-treatment. ΔIPSS score inversely correlated with disease duration. CONCLUSIONS: This results support previous evidence of pathophysiological involvement of dopaminergic transmission on bladder dysfunction in PD.

Italian recommendations for the diagnosis and treatment of myasthenia gravis.

Myasthenia gravis is a well-treatable disease, in which a prompt diagnosis and an adequate management can achieve satisfactory control of symptoms in the great majority of patients. Improved knowledge of the disease pathogenesis has led to recognition of patient subgroups, according to associated antibodies, age at onset and thymus pathology, and to a more personalized treatment. When myasthenia gravis is suspected on clinical grounds, diagnostic confirmation relies mainly on the detection of specific antibodies. Neurophysiological studies and, to a lesser extent, clinical response to cholinesterase inhibitors support the diagnosis in seronegative patients. In these cases, the differentiation from congenital myasthenia can be challenging. Treatment planning must consider weakness extension and severity, disease subtype, thymus pathology, together with patient characteristics and comorbidities. Since most subjects with myasthenia gravis require long-term immunosuppressive therapy, surveillance of expected and potential adverse events is critical. For patients refractory to conventional immunosuppression, the use of biologic agents is highly promising. These recommendations are addressed to non-experts on neuromuscular transmission disorders. The diagnostic procedures and therapeutic approaches hereafter described are largely accessible in Italy.

Rotigotine Effects on Bladder Function in Patients with Parkinson's Disease.

BACKGROUND: The objective of this study was to assess the effect of rotigotine treatment on bladder function in patients with Parkinson's disease (PD) who have urinary urgency. METHODS: in total, 20 patients with PD underwent urodynamic evaluation and completed International Prostate Symptoms questionnaires in off-rotigotine condition and after 3 months of rotigotine patch monotherapy administration. In both sessions, clinical motor condition was evaluated with the Unified Parkinson Disease Rating Scale, Part III (motor part). RESULTS: Rotigotine administration significantly ameliorated the first sensation of bladder filling, the neurogenic detrusor overactive contractions threshold and bladder capacity compared with the off-treatment condition. Moreover, the total score on the International Prostate Symptoms questionnaire revealed a decrease of filling (irritative) symptoms after rotigotine treatment compared with the off-treatment condition. CONCLUSION: The positive effects of rotigotine may be due to its balanced agonism to D1 and D2 receptors and in particular to its stimulation of D1 receptors in the anterior cingulate cortex and insula, which are known as areas involved in bladder-inhibitory functions.

Theta burst stimulation modulates cerebellar-cortical connectivity in patients with progressive supranuclear palsy.

BACKGROUND: Progressive Supranuclear Palsy (PSP) is an atypical degenerative Parkinsonism characterized by postural instability, supranuclear gaze palsy and frontal deficits. Recent imaging studies revealed that the volume of cerebellar peduncles and midbrain were reduced in PSP. Transcranial magnetic stimulation (TMS) studies demonstrated a cerebellar involvement in PSP showing an impairment of functional connectivity between the cerebellar hemisphere (Cb) and the contralateral primary motor cortex (M1) (cerebellar brain inhibition-CBI). OBJECTIVE: To investigate the plasticity of the cerebello-thalamo-cortical circuits in ten PSP patients after two-week course of cerebellar intermittent theta burst stimulation (iTBS), a form of repetitive TMS. METHODS: Before and after the iTBS sessions we measured functional connectivity between Cb and contralateral M1 (CBI), short intracortical inhibition (SICI) and intracortical facilitation (ICF) and short latency afferent inhibition (SLAI) in contralateral M1. We also performed resting state functional magnetic resonance (rs-fMRI) and we administered clinical rating scale (PSP-RS). RESULTS: At baseline PSP patients had decreased efficiency of CBI, SICI and SLAI in comparison to PD patients and healthy subjects. Cerebellar iTBS increased the deficient functional cerebellar-motor connectivity as assessed by CBI. No effect was seen for SICI/ICF and SLAI circuits. Following iTBS there was an increased signal in the head of the caudate nucleus bilaterally as shown by rs-fMRI. Moreover, PSP-RS showed an improvement of dysarthria in all patients. CONCLUSIONS: iTBS enhanced functional connectivity between the cerebellar hemisphere, the caudate nucleus and the cortex, that was paralleled by some clinical improvement. Future randomized, sham-stimulation controlled studies are warranted to support the clinical efficacy of this technique.

A relationship between bruxism and orofacial-dystonia? A trigeminal electrophysiological approach in a case report of pineal cavernoma.

BACKGROUND: In some clinical cases, bruxism may be correlated to central nervous system hyperexcitability, suggesting that bruxism may represent a subclinical form of dystonia. To examine this hypothesis, we performed an electrophysiological evaluation of the excitability of the trigeminal nervous system in a patient affected by pineal cavernoma with pain symptoms in the orofacial region and pronounced bruxism. METHODS: Electrophysiological studies included bilateral electrical transcranial stimulation of the trigeminal roots, analysis of the jaw jerk reflex, recovery cycle of masseter inhibitory reflex, and a magnetic resonance imaging study of the brain. RESULTS: The neuromuscular responses of the left- and right-side bilateral trigeminal motor potentials showed a high degree of symmetry in latency (1.92 ms and 1.96 ms, respectively) and amplitude (11 mV and 11.4 mV, respectively), whereas the jaw jerk reflex amplitude of the right and left masseters was 5.1 mV and 8.9 mV, respectively. The test stimulus for the recovery cycle of masseter inhibitory reflex evoked both silent periods at an interstimulus interval of 150 ms. The duration of the second silent period evoked by the test stimulus was 61 ms and 54 ms on the right and left masseters, respectively, which was greater than that evoked by the conditioning stimulus (39 ms and 35 ms, respectively). CONCLUSIONS: We found evidence of activation and peripheral sensitization of the nociceptive fibers, the primary and secondary nociceptive neurons in the central nervous system, and the endogenous pain control systems (including both the inhibitory and facilitatory processes), in the tested subject. These data suggest that bruxism and central orofacial pain can coexist, but are two independent symptoms, which may explain why numerous experimental and clinical studies fail to reach unequivocal conclusions.

The effect of dopamine agonists on cognitive functions in non-demented early-mild Parkinson's disease patients.

The effect of dopamine agonists (DAs) on cognition in Parkinson's disease (PD) is not yet completely established. Previous papers reported a worsening effect on some cognitive functions with some DAs, but not with others, suggesting that DAs may differently affect cognition in PD patients according to their pharmacological characteristics. We set out to test the effect of rotigotine and cabergoline on cognitive functions in a group of forty non-demented early-mild PD patients (H &Y <2). Subjects were randomly divided into two groups and evaluated in a randomized cross-over study using neuropsychological tests; at the same time, motor function was monitored under three different treatment conditions: DA (rotigotine or cabergoline), L-dopa, and off therapy. Rotigotine and cabergoline were chosen because while they share a mixed D1 and D2 receptor profile, the former is non-ergolinic and the latter ergolinic. No significant differences were found in cognitive function between the basal condition and the DA treatments. On the basis of the present data, which we compare with previous findings regarding pramipexole IR and pergolide, we hypothesize that combined stimulation of both dopamine receptor families, as occurs with rotigotine, cabergoline, L-dopa and pergolide, may preserve cognitive functions more than pure D2 family stimulation.

Metabolic changes induced by theta burst stimulation of the cerebellum in dyskinetic Parkinson's disease patients.

BACKGROUND: Cerebellar repetitive transcranial magnetic stimulation may be effective in reducing peak-dose levodopa induced dyskinesia in Parkinson's disease patients. It was proposed that the antidyskinetic effect could be due to modulation of cerebello-thalamo-cortical pathways. However the neural basis for these clinical effects have not yet been demonstrated. METHODS: We investigated the effects of repeated sessions of cerebellar continuous theta burst stimulation in Parkinson's disease patients with levodopa induced dyskinesia on brain metabolism by means of positron emission tomography scan with fluorodeoxyglucose ((18)F-FDG) to characterize the specific cerebral network activated by cerebellar stimulation in these patients. RESULTS: We found that five days of bilateral cerebellar continuous theta burst stimulation (cTBS) were effective in reducing levodopa induced dyskinesia. Clinical changes were paralleled by a reduction of (18)F-FDG metabolism in the cerebellum as revealed by positron emission tomography imaging. We found a global decrease in the metabolism of the bilateral cerebellar hemispheres, and a significant decrease in (18)F-FDG uptake in correspondence of bilateral dentate nucleus. CONCLUSIONS: Our study demonstrates the antidyskinetic effect of cerebellar cTBS in Parkinson's disease patients with levodopa induced dyskinesia, is paralleled by modulation of the activity of the pathways connecting the cerebellar cortex with the deep cerebellar nuclei, confirming the hypothesis that the motor cerebellar circuit is involved in the generations of levodopa induced dyskinesia.

Bladder symptoms assessed with overactive bladder questionnaire in Parkinson's disease.

In Parkinson's disease (PD) the urinary dysfunction manifests primarily with symptoms of overactive bladder (OAB). The OAB questionnaire (OAB-q) is a measure designed to assess the impact of OAB symptoms on health-related quality of life. In this study, we quantified the urinary symptoms in a large cohort of PD patients by using the OAB-q short form. Possible correlations between the OAB-q and clinical features were tested. Three hundred and two PD patients were enrolled in the study. Correlations between the OAB-q and sex, age, Unified Parkinson's Disease Rating Scale part III (UPDRS-III), Hoehn-Yahr (H-Y) staging, disease duration, and treatment were analyzed. Data were compared with a large cohort of 303 age-matched healthy subjects. The OAB-q yielded significantly higher scores in PD patients than in healthy subjects. In the group of PD patients, all the variables tested were similar between men and women. Pearson's coefficient showed a significant correlation between mean age, disease duration, mean OAB-q scores, UPDRS-III scores, and H-Y staging. A multiple linear regression analysis showed that OAB-q values were significantly influenced by age and UPDRS-III. No statistical correlations were found between OAB-q scores and drug therapy or the equivalent levodopa dose, whilst the items relating to the nocturia symptoms were significantly associated with the equivalent levodopa dose. Our findings suggest that bladder dysfunction assessed by OAB-q mainly correlates with UPDRS-III scores for severity of motor impairment, possibly reflecting the known role of the decline in nigrostriatal dopaminergic function in bladder dysfunction associated with PD and patients' age. Our study also suggests that the OAB-q is a simple, easily administered test that can objectively evaluate bladder function in patients with PD.

Non-motor functions in parkinsonian patients implanted in the pedunculopontine nucleus: focus on sleep and cognitive domains.

Between 2005 and 2007, six patients affected by idiopathic Parkinson's disease (IPD) were submitted to the bilateral implantation (and subsequent deep brain stimulation - DBS) of the pedunculopontine nucleus (PPN) plus the subthalamic nucleus (STN). This review synthesizes the effects of PPN low-frequency stimulation on non-motor functions, focusing on patient sleep quality and cognitive performance. If not associated to STN-DBS, PPN-DBS promoted a modest amelioration of patient motor performance. However, during PPN-DBS, they experienced on the one hand a significant improvement in executive functions and working memory, on the other hand a beneficial change in sleep architecture. Overall, the limited sample hampers definite conclusions. Yet, although the PPN-DBS induced motor effects are quite disappointing (discouraging extended trials based upon the sole PPN implantation), the neuropsychological profile supports the contention by which in selected PD patients, with subtle cognitive deficits or vanished efficacy of previous implanted STN, PPN-DBS might still represent a reliable and compassionate option.

Usefulness of transcatheter patent foramen ovale closure in migraineurs with moderate to large right-to-left shunt and instrumental evidence of cerebrovascular damage.

Transcatheter patent foramen ovale (PFO) closure might be effective in improving migraines. To assess the efficacy of PFO closure in migraineurs with a moderate to large right-to-left shunt and instrumental evidence of embolic cerebral damage, 76 highly symptomatic migraineurs were prospectively investigated. The presenting clinical syndrome was stroke in 16 patients, repeated transient ischemic attack in 32 patients, and lone migraine associated with cerebral ischemic lesions on magnetic resonance imaging in 28 patients. Migraine severity was assessed before PFO closure and monthly for 6 months after discontinuation of antiplatelet therapy. At the end of 12 months of follow-up, the averaged postprocedural total score was compared with the baseline score. Transcatheter PFO closure was successful in all patients, and the 12-month PFO closure rate was 97%. The baseline total migraine score was similar in patients with stroke, transient ischemic attack, and lone migraine (6.8 +/- 1.6, 6.7 +/- 1.4, and 6.9 +/- 1.7 respectively, p = NS). After a mean follow-up of 13.7 +/- 2.4 months, no recurrent cerebrovascular episodes had occurred. At the end of the follow-up period, a significant reduction in the total migraine score was observed in all groups, regardless of the initial clinical presentation. Migraine was completely abolished in 35 patients (46%), improved in 27 (36%), and unchanged in 14 (18%). The proportion of patients with migraine suppression and improvement was similar in the 3 groups. In conclusion, in highly symptomatic migraineurs with previous ischemic cerebral events and instrumental evidence of cerebral embolism, transcatheter PFO closure can result in improvement of migraine severity in a high percentage of patients.

Effects of inhibitory rTMS on bladder function in Parkinson's disease patients.

Patients affected by Parkinson's disease (PD) may present with lower urinary tract (LUT) dysfunction characterized by involuntary detrusor overactivity. We evaluated possible impact of a 2-week course of low frequency 1 Hz repetitive transcranial magnetic stimulation (rTMS) on LUT behavior in eight advanced PD patients complaining of urinary disturbances. We tested the effects of rTMS measuring urodynamic examination and the International Prostate Symptoms Score (IPSS) questionnaire, used for evaluation of subjective LUTS. rTMS was able to improve temporarily LUT behavior in PD patients, increasing bladder capacity and the first sensation of filling phase. Moreover, a reduction of IPSS score was noticed, due to an improvement on filling phase symptoms. The beneficial effects assessed with the IPSS lasted for up to 2 weeks after the end of the stimulation. rTMS seems to be an effective, noninvasive alternative treatment for PD patients with urinary disturbances.

Cellular and humoral immune alterations in thymectomized patients for thymoma.

The aim of this study was to analyze the impact of thymectomy on kinetics of the immune reconstitution in thymoma patients. Nine consecutive patients with completely resected thymoma were enrolled. Immunophenotype analysis (total lymphocytes, CD3, CD4, CD8, CD19, NK subsets) and detection of autoantibodies at 6, 12, 18, and 24 months after thymectomy were planned. A prolonged inversion of CD4/CD8 ratio was present, due to a diminished number of CD4+ cells; CD8+ cell numbers remaining constantly normal at different time points; CD19+ cells remained for a long time understatement, achieving almost normal levels at 24 months; and NK cells always showed a normal amount. Autoantibodies against the muscle acetylcholine receptor were detected in four patients (44.4%) at the time of diagnosis, while antinuclear antibody were detected in eight patients (88.8%) at different time points during postthymectomy. A high incidence of multiple primary neoplasms was observed (66.6% of cases). Our study showed that cellular and humoral immune alterations are a common sequelae of postthymectomy. Further studies, a longer surveillance and a cooperative approach, due to the rarity of the disease, are necessary to define eventual implications of immune alterations on patient's outcome.

Treatment of the symptoms of Huntington's disease: preliminary results comparing aripiprazole and tetrabenazine.

Aripiprazole (AP), a dopamine (DA) D(2) receptor partial agonist, has recently been used to reduce schizophrenic symptoms, while tetrabenazine (TBZ), a DA depletor, has been used to treat hyperkinesias in Huntington's disease (HD). The aim of this study is to define the role of AP on chorea, motor performance, and functional disability, and to compare the effects of AP vs. TBZ in a small study of six patients with HD. Both AP and TBZ increased the Unified Huntington's Disease Rating Scale (UHDRS) chorea score in a similar way. However, AP caused less sedation and sleepiness than TBZ and was better tolerated by the patients on the trial. Moreover, AP showed a slight but not significant improvement of depression in the patients as compared to TBZ. A larger group of patients and a longer period of observation are an important prerequisite for further evaluations of AP's therapeutic use.