Internuclear Ophthalmoplegia as an Isolated Symptom of Brainstem Wake-up Stroke Responsive to Intravenous Thrombolysis: Evidence from MRI.

BACKGROUND: Internuclear ophthalmoplegia (INO) is a disorder of eye movements caused by a lesion involving the medial longitudinal fasciculus (MLF) within the brainstem, and it is characterized by adduction impairment combined with contralateral dissociated abduction nystagmus. The frequency of acute ischemic stroke (AIS) presenting with INO as a predominant symptom is very low, and many patients suffering from this brainstem AIS are precluded from intravenous thrombolysis (IVT). OBJECTIVE: To provide for the first time a magnetic resonance imaging (MRI) evidence of response to the IVT in brainstem wake-up stroke presenting with INO as an isolated symptom. METHODS: Here, we described a rare case of pons AIS presenting with INO as a unique symptom of awakening. In order to differentiate an ischemic stroke from other stroke mimics, and to determine whether the patient was within the therapeutic window for IVT (wake-up stroke), brain MRI including DWI and FLAIR sequences was acquired. RESULTS: A left paramedian pontine DWI/FLAIR mismatch was detected and the patient was considered eligible for IVT. After IVT, the patient made a full recovery with complete resolution of INO. Follow-up MRI at 1 month demonstrates the absence of ischemic lesions. CONCLUSION: Our case provides neuroradiological evidence of IVT efficacy in brainstem stroke, and it should prompt clinicians to rapidly perform MRI in wake-up onset INO and to just as quickly administer IVT, since INO is a functionally disabling deficit. Finally, this case demonstrates the value of MRI in diagnostic, prognostic, and therapeutic workup of posterior circulation wake-up stroke.

Recurrent Miller-Fisher syndrome overlapping Guillain-Barrè syndrome and Bickerstaff brainstem encephalitis: A case report.

Miller-Fisher syndrome (MFS) together with Guillan-Barré syndrome (GBS) and Bickerstaff brainstem encephalitis (BBE) are considered to form a continuous clinical spectrum of the same disease, possibly affecting the peripheral and/or central nervous systems, with monophasic symptoms. The frequency of overlapping clinical signs and the risk of recurrence are independent and very low, but no cases of GQ1b-seropositive recurrent MFS overlapping with GBS and BBE have been described so far. Here, we describe for the first time an atypical case of recurrent GQ1b-seropositive MFS overlapping GBS and BBE, 12 years after a previous GQ1b-seronegative typical MFS episode. Our case expands the clinical spectrum of recurrent MFS, and it should prompt clinicians to investigate the presence of anti-ganglioside antibodies in recurrent MFS even when these were negative in the previous episode, especially in those presenting with overlapping spectrum symptoms and a critically ill picture during the second episode.

Intracellular FMRpolyG-Hsp70 complex in fibroblast cells from a patient affected by fragile X tremor ataxia syndrome.

BACKGROUND: Fragile X-associated tremor/ataxia syndrome is a late-onset neurodegenerative disorder that affects about 40% of carriers of CGG-repeat expansions in the premutation range within the fragile X gene (FMR1). Main clinical features include intention tremor, cerebellar ataxia, and parkinsonism. Recently, great emphasis on the deposition of soluble aggregates produced by a RAN translation process, as main pathogenic mechanism, has been given. These aggregates contain a small protein with a polyglycine stretch on the aminoterminal end named FMRpolyG and, so far, have been isolated and characterized in drosophila and mouse models, in post mortem brain of fragile X-associated tremor/ataxia syndrome patients, in fibroblasts of fragile primary ovarian insufficiency patients, but never in fibroblasts from a fragile X-associated tremor/ataxia living patients. In adult carriers the syndrome is frequently misdiagnosed due to the lack of specific markers. METHODS: We standardized immunocytochemistry, immunoprecipitation and western blot procedures to study and biochemically characterize the FMRpolyG protein in fibroblasts from human skin biopsy. RESULTS: We demonstrate for the first time, in fibroblasts from a patient affected by Fragile X-associated tremor/ataxia syndrome, the presence ex vivo of inclusions consisting of FMRpolyG- Hsp70 soluble aggregates. CONCLUSION: These observations can pave the way to develop a cellular model for studying ex vivo and in vitro the mechanisms involved in the production of FMRpolyG aggregates, their toxicity, and the role of the FMRpolyG-Hsp70 interaction in the pathogenesis of fragile X-associated tremor/ataxia syndrome.

Clinical, electrophysiological, and imaging study in essential tremor-Parkinson's disease syndrome.

INTRODUCTION: Essential tremor-Parkinson's disease (ET-PD) syndrome is a clinical condition in which individuals with a long-lasting history of Essential tremor (ET) eventually develop Parkinson's disease (PD). The aim of the study was to investigate the accuracy performances of clinical, neurophysiological, and imaging biomarkers in differentiating patients affected by ET-PD syndrome from patients with ET or PD. METHODS: Nineteen patients affected by ET-PD syndrome, 48 ET patients, and 37 tremor-dominant PD (t-PD) patients were included. Electrophysiological studies, including blink-reflex recovery cycle and tremor parameters analyses, were performed in all groups. Nigro-striatal and cardiac sympathetic denervation were also investigated. Sensitivity, specificity and accuracy of clinical, electrophysiological, and radiological features in differentiating ET-PD syndrome from ET and PD were calculated. RESULTS: ET-PD patients had significantly lower rigidity (p = 0.007) and higher postural/kinetic tremor (p = 0.007) scores, in comparison to t-PD patients. ET-PD patients, differently from PD patients, had a synchronous pattern of resting tremor and, differently from ET patients, had abnormal blink-reflex recovery cycle. ET-PD patients also showed reduced nigro-striatal and cardiac sympathetic uptakes, albeit to a lesser extent than in PD patients. The highest accuracy values were found for the synchronous pattern of resting tremor (97.1%) in distinguishing ET-PD from PD, and for presence of abnormal blink-recovery cycle (100%) in distinguishing ET-PD syndrome from ET. CONCLUSION: Our study demonstrates that some electrophysiological parameters, such as a synchronous resting tremor pattern and the abnormal blink-recovery cycle were the most accurate biomarkers in distinguishing patient with ET-PD syndrome from those with ET or those with PD.

Processing graspable object images and their nouns is impaired in Parkinson's disease patients.

According to embodiment, the recruitment of the motor system is necessary to process language material expressing a motor content. Coherently, an impairment of the motor system should affect the capacity to process language items with a motor content. The aim of the present study was to assess the capacity to process graspable objects and their nouns in Parkinson's disease (PD) patients and healthy controls. Participants saw photos and nouns depicting graspable and non-graspable objects. Scrambled images and pseudo-words served as control stimuli. At 150 msec after stimulus presentation, they had to respond when the stimulus referred to a real object, and refrain from responding when it was meaningless (go-no go paradigm). In the control group, participants gave slower motor responses for stimuli (both photos and nouns) related to graspable objects as compared to non-graspable ones. This in keeping with data obtained in a previous study with young healthy participants. In the PD group, motor responses were similar for both graspable and non-graspable items. Moreover, error number was significantly greater than in controls. These findings support the notion that when the motor circuits are lesioned, like in PD, patients do not show the typical modulation of motor responses and have troubles in processing graspable objects and their nouns.

Structural connectivity differences in essential tremor with and without resting tremor.

In this work, we investigated motor network structure in patients affected by essential tremor (ET) with or without resting tremor, using probabilistic tractography of the cerebello-thalamo-basal ganglia-cortical loop. Twenty-five patients with ET, twenty-two patients with ET associated with resting tremor (rET), and twenty-five age- and sex-matched healthy controls were included in the study. All participants underwent whole-brain 3D T1-weighted and diffusion-weighted MRI, and DAT-SPECT. Probabilistic tractography was performed on diffusion data in network mode, reconstructing connections between the different structures of the cerebello-thalamo-basal ganglia-cortical loop. All patients with ET, regardless of the presence of resting tremor, had normal DAT-SPECT, but showed significantly decreased connectivity in the cerebello-thalamo-precentral cortex network bilaterally, compared to healthy controls. In addition, patients with rET showed reduced connectivity in a pathway connecting globus pallidus, caudate, and supplementary motor area, compared to ET and controls. This latter circuit was significantly damaged in the hemisphere contralateral to the side clinically most affected by resting tremor. These findings provide insights upon structural changes underlying the different clinical presentations of ET. Our study demonstrates that ET and rET share common alterations in the cerebello-thalamo-precentral cortex circuit, while rET patients are characterized by specific damage to additional structures of motor network, such as globus pallidus, caudate nucleus, and supplementary motor area. Our findings suggest that ET and rET are different subtypes of the same neurodegenerative disorder.

Structural connectivity differences in motor network between tremor-dominant and nontremor Parkinson's disease.

Motor phenotypes of Parkinson's disease (PD) are recognized to have different prognosis and therapeutic response, but the neural basis for this clinical heterogeneity remains largely unknown. The main aim of this study was to compare differences in structural connectivity metrics of the main motor network between tremor-dominant and nontremor PD phenotypes (TD-PD and NT-PD, respectively) using probabilistic tractography-based network analysis. A total of 63 PD patients (35 TD-PD patients and 28 NT-PD patients) and 30 healthy controls underwent a 3 T MRI. Next, probabilistic tractography-based network analysis was performed to assess structural connectivity in cerebello-thalamo-basal ganglia-cortical circuits, by measuring the connectivity indices of each tract and the efficiency of each node. Furthermore, dopamine transporter single-photon emission computed tomography (DAT-SPECT) with 123 I-ioflupane was used to assess dopaminergic striatal depletion in all PD patients. Both PD phenotypes showed nodal abnormalities in the substantia nigra, in agreement with DAT-SPECT evaluation. In addition, NT-PD patients displayed connectivity alterations in nigro-pallidal and fronto-striatal pathways, compared with both controls and TD-PD patients, in which the same motor connections seemed to be relatively spared. Of note, in NT-PD group, rigidity-bradykinesia score correlated with fronto-striatal connectivity abnormalities. These findings demonstrate that structural connectivity alterations occur in the cortico-basal ganglia circuit of NT-PD patients, but not in TD-PD patients, suggesting that these anatomical differences may underlie different motor phenotypes of PD. Hum Brain Mapp 38:4716-4729, 2017. © 2017 Wiley Periodicals, Inc.

Heart rate variability in patients with essential tremor: A cross sectional study.

OBJECTIVE: To investigate heart rate variability (HRV) in patients with Essential Tremor (ET) in comparison with patients with Parkinson's Disease (PD). METHODS: This is a cross sectional control study including 10 patients with ET, 10 patients with PD and 10 age-sex-matched controls. In patients and controls, we measured the components of HRV analysis in the frequency domain during a daytime period of 12-h. Selected HRV variables were low-frequency (LF) and high-frequency (HF), conventionally considered to be influenced by the sympathetic system and the parasympathetic system respectively. RESULTS: HRV variables, in patients with ET, were significantly different from those detected in PD patients and similar to those of controls while in PD patients, they were significantly different from those of controls. At cut off level of 654 ms2, LF component correctly distinguished ET patients versus PD with sensitivity, specificity, PPV and accuracy of 100%. By contrast, at cut off level of 737 ms2, HF component showed sensitivity, specificity, PPV and accuracy of 80%, 100%, 100%, and 86.67% respectively. DAT-SPECT and cardiac MIBG uptake were both normal in ET patients whereas they were markedly decreased in those with PD. CONCLUSIONS: In our study, the LF component of HRV analysis distinguishes ET patients from those with PD on an individual basis, thus representing a valid help in everyday clinical practice for differentiation between these patients in absence of scintigraphic investigations.

Alterations of putaminal shape in de novo Parkinson's disease.

INTRODUCTION: Several neuroimaging studies have been carried out to gain insight on the pathological processes that cause PD, but literature findings are inconsistent. The aim of this study was to combine information carried by functional imaging with DA transporter ligands and structural MRI. METHODS: Forty-two untreated, de novo-PD patients and 30 control subjects were involved in this study. Patients were divided in subgroups according to the presence of uni- or bilateral reduction of ligand uptake in the putamen, as observed on DA transporter single-photon emission tomography: 12 patients had abnormal uptake in the right putamen and 11 in the left, whereas 19 had bilateral abnormal uptake. Voxel-based morphometry and shape analysis were used to compare healthy subjects to all de novo-PD or to patients with either right or left abnormal uptake. RESULTS: Shape analysis identified significant differences between de novo-PD and controls in putaminal regions. In patients with unilateral abnormal uptake, only the medial surface of the structure was involved. When patients with bilateral uptake reduction were also considered, changes extended from the medial to the lateral surface of putamina. Voxel-based morphometry showed similar results to those detected with shape analysis, but it failed to identify the putaminal subfield involved in patients with asymmetric or symmetric damage on DA transporter single-photon emission tomography. CONCLUSIONS: Shape analysis in de novo-PD patients suggested a progressive medial-to-lateral involvement of the putamina that paralleled an asymmetric-to-bilateral distribution of DA transporter depletion. © 2016 International Parkinson and Movement Disorder Society.

[Home exercise therapy in chronic congestive heart failure: observational study of factors affecting adherence to the program]. / Training fisico domiciliare nello scompenso cardiaco cronico: studio osservazionale sui fattori condizionanti l'aderenza al programma.

BACKGROUND: Physical training has proven to be a valid and effective therapeutic tool capable of counteracting muscle changes that occur in chronic heart failure (CHF) patients. Nevertheless, few studies have analyzed the frequency of use of this therapy and the reasons for any reduced compliance and adherence to the prescription. The aim of this study was to quantify the frequency of the participation of CHF patients in a program of domiciliary physical training and to analyze the factors that can influence adherence to the program. METHODS: Three hundred and twenty-two consecutive CHF patients (ejection fraction 28 +/- 7%) in a stable condition with optimized medical therapy performed a cardiopulmonary test, including determination of peak oxygen consumption, at baseline and after 9 +/- 3 months. All the patients had participated in sessions of health education on the relationship between illness/physical activity. The prescription of physiotherapy was decided by the physician on the basis of each patient's clinical need assessed in the diagnostic-therapeutic management. The patient referred for physiotherapy entered a therapeutic strategy that included sessions of training on anaerobic threshold, self-management of the session, and formulation of a domiciliary physical training program. During the follow-up evaluation the patients were asked to complete a questionnaire, which investigated the relationship between several factors and the patient's adherence to the physical training program, which was objectively evaluated by the change in peak oxygen consumption recorded at the end of the training, taking into account the spontaneous variations found in the control group. RESULTS: Two hundred and eighty-two of the patients (88%) satisfied the criteria for inclusion in the study. Only 61 (22%) of them were judged to have adhered to the recommended physical training. Type of employment (chi 2 = 7.08, p < 0.02), the state of retirement (chi 2 = 8.9, p < 0.01), ischemic etiology (chi 2 = 5.91, p < 0.01), compatibility with employment (chi 2 = 15.8, p < 0.0004), availability of suitable domestic conditions (chi 2 = 14.5, p < 0.0008), the structure of the training program (chi 2 = 22.33, p < 0.0001) and a learning phase in a gym (chi 2 = 71.33, p < 0.0001) were significantly correlated at univariate analysis with the performance of the physical training. Multivariate analysis identified the structure of the training program (odds ratio 9.6, 95% confidence interval 2.8-33) and a learning phase in a gym (odds ratio 49.6, 95% confidence interval 11-210.8) as independent factors (r2 = 0.48) determining adherence to the physical training program. CONCLUSIONS: Adherence to unmonitored, recommended domiciliary physical training appears to be modest even in patients who have been in-patients in a cardiac rehabilitation center. Various factors seem to influence the adherence of the patient to this therapy, but structural factors, such as the organization and learning of the program, more strongly influenced the patient's subsequent compliance.