The Minor's test in Frey syndrome treated with botulinum toxin: Methodology and efficacy.

In this paper, we aimed at methodologically presenting a video-case of Frey Syndrome occurred after parotidectomy, assessed by means of Minor's Test and treated with intradermic botulinum toxin A (BoNT-A) injection. Although largely described in the literature, a detailed explanation of both the procedures has not been previously elucidated. In a more original approach, we also highlighted the role of the Minor's test in identifying the most affected skin areas and new insight on the patient-tailored approach provided by multiple injections of botulinum toxin. Six months after the procedure, the patient's symptoms were resolved, and no evident signs of Frey syndrome were detectable through the Minor's test.

Assessment of neurological manifestations in hospitalized patients with COVID-19.

BACKGROUND AND PURPOSE: The objective of this study was to assess the neurological manifestations in a series of consecutive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients, comparing their frequency with a population hospitalized in the same period for flu/respiratory symptoms, finally not related to SARS-CoV-2. METHODS: Patients with flu/respiratory symptoms admitted to Fondazione Policlinico Gemelli hospital from 14 March 2020 to 20 April 2020 were retrospectively enrolled. The frequency of neurological manifestations of patients with SARS-CoV-2 infection was compared with a control group. RESULTS: In all, 213 patients were found to be positive for SARS-CoV-2, after reverse transcriptase polymerase chain reaction on nasal or throat swabs, whilst 218 patients were found to be negative and were used as a control group. Regarding central nervous system manifestations, in SARS-CoV-2-positive patients a higher frequency of headache, hyposmia and encephalopathy always related to systemic conditions (fever or hypoxia) was observed. Furthermore, muscular involvement was more frequent in SARS-CoV-2 infection. CONCLUSIONS: Patients with COVID-19 commonly have neurological manifestations but only hyposmia and muscle involvement seem more frequent compared with other flu diseases.

Spread of dystonia in patients with idiopathic adult-onset laryngeal dystonia.

BACKGROUND AND PURPOSE: Adult-onset laryngeal dystonia (LD) can be isolated or can be associated with dystonia in other body parts. Combined forms can be segmental at the onset or can result from dystonia spread to or from the larynx. The aim of this study was to identify the main clinical and demographic features of adult-onset idiopathic LD in an Italian population with special focus on dystonia spread. METHODS: Data were obtained from the Italian Dystonia Registry (IDR) produced by 37 Italian institutions. Clinical and demographic data of 71 patients with idiopathic adult-onset LD were extracted from a pool of 1131 subjects included in the IDR. RESULTS: Fifty of 71 patients presented a laryngeal focal onset; the remaining subjects had onset in other body regions and later laryngeal spread. The two groups did not show significant differences of demographic features. 32% of patients with laryngeal onset reported spread to contiguous body regions afterwards and in most cases (12 of 16 subjects) dystonia started to spread within 1 year from the onset. LD patients who remained focal and those who had dystonia spread did not show other differences. CONCLUSIONS: Data from IDR show that dystonic patients with focal laryngeal onset will present spread in almost one-third of cases. Spread from the larynx occurs early and is directed to contiguous body regions showing similarities with clinical progression of blepharospasm. This study gives a new accurate description of LD phenomenology that may contribute to improving the comprehension of dystonia pathophysiology.

Non-equilibrium phase transition in a model for supercoiling-dependent DNA transcription.

We study a variant of a recently proposed non-equilibrium stochastic model for supercoiling-dependent transcription in DNA. In the case of a circular DNA molecule with overall positive supercoiling, we find a non-equilibrium phase transition between an absorbing phase, where all genes are switched off due to the supercoiling, and an active phase with a non-zero transcription rate. Mean field theory predicts that the transition should be continuous at a critical value of the background supercoiling, and we focus our analysis on this case. Our simulations suggest that the switch between the transcribed and silent phases may actually be a fluctuation-induced discontinuous transition, where the jump in the transcription rate decreases with the number of genes in the system.

Correction to: The Italian Dystonia Registry: rationale, design and preliminary findings.

In the original article, Gina Ferrazzano was affiliated to Department of Neurology and Psychiatry, Neuromed Institute IRCCS, Sapienza University of Rome, Pozzilli, Italy.The corrected affiliation should be: Neuromed Institute IRCCS, Pozzilli, IS, Italy.

DJ-1 modulates mitochondrial response to oxidative stress: clues from a novel diagnosis of PARK7.

DJ-1 mutations are associated to early-onset Parkinson's disease and accounts for about 1-2% of the genetic forms. The protein is involved in many biological processes and its role in mitochondrial regulation is gaining great interest, even if its function in mitochondria is still unclear. We describe a 47-year-old woman affected by a multisystem disorder characterized by progressive, early-onset parkinsonism plus distal spinal amyotrophy, cataracts and sensory-neural deafness associated with a novel homozygous c.461C>A [p.T154K] mutation in DJ-1. Patient's cultured fibroblasts showed low ATP synthesis, high ROS levels and reduced amount of some subunits of mitochondrial complex I; biomarkers of oxidative stress also resulted abnormal in patient's blood. The clinical pattern of multisystem involvement and the biochemical findings in our patient highlight the role for DJ-1 in modulating mitochondrial response against oxidative stress.

The Italian Dystonia Registry: rationale, design and preliminary findings.

The Italian Dystonia Registry is a multicenter data collection system that will prospectively assess the phenomenology and natural history of adult-onset dystonia and will serve as a basis for future etiological, pathophysiological and therapeutic studies. In the first 6 months of activity, 20 movement disorders Italian centres have adhered to the registry and 664 patients have been recruited. Baseline historical information from this cohort provides the first general overview of adult-onset dystonia in Italy. The cohort was characterized by a lower education level than the Italian population, and most patients were employed as artisans, builders, farmers, or unskilled workers. The clinical features of our sample confirmed the peculiar characteristics of adult-onset dystonia, i.e. gender preference, peak age at onset in the sixth decade, predominance of cervical dystonia and blepharospasm over the other focal dystonias, and a tendency to spread to adjacent body parts, The sample also confirmed the association between eye symptoms and blepharospasm, whereas no clear association emerged between extracranial injury and dystonia in a body site. Adult-onset dystonia patients and the Italian population shared similar burden of arterial hypertension, type 2 diabetes, coronary heart disease, dyslipidemia, and hypothyroidism, while hyperthyroidism was more frequent in the dystonia population. Geographic stratification of the study population yielded no major difference in the most clinical and phenomenological features of dystonia. Analysis of baseline information from recruited patients indicates that the Italian Dystonia Registry may be a useful tool to capture the real world clinical practice of physicians that visit dystonia patients.

New olfactometric findings in Parkinson's disease.

OBJECTIVES: To investigate in Parkinson's disease-affected patients a correlation between hyposmia and gastrointestinal dysfunction and their possible identical etiopathogenesis. DESIGN: Retrospective cohort study. SETTING: ENT and neurology departments (Gemelli Hospital, Rome, Italy). PARTICIPANTS: A total of 78 patients with diagnosis of PD according to the UK Brain Bank criteria. INCLUSION CRITERIA: informed consent and olfactory testing executed; exclusion criteria: signs of dementia according to the DSM-IV criteria; Mini Mental State Examination score ≤26; head trauma; central neurological disorders, nasal or systemic diseases potentially affecting olfactory function. Motor condition was assessed by means of Hoehn and Yahr staging and by section III of the Unified PD Rating Scale, performed off and on medications. MAIN OUTCOME MEASURES: The patients underwent olfactory evaluation (TDI score), after rhinomanometry with nasal decongestion. A total of 25 non-motor symptoms were evaluated through an interview. RESULTS: Olfactory dysfunction was objectively found in 91.0% of patients, a percentage higher than the subjective hyposmia reported (55.1%) P = 0.0001. Seven patients (9.0%) were normosmic, 49 (62.8%) hyposmic and 22 (28.2%) anosmic. Subjective hyposmia, constipation, bloating and dyspepsia differed across groups, being higher in anosmic and hyposmic ones than in the normosmic group. P value was ≤0.05 for each symptom. Despite the original results, this study has the limitation of being based on subjective ratings by a relatively limited group of patients. CONCLUSIONS: Hyposmia and gastrointestinal symptoms are correlated, and this would support a possible common origin; the CNS could be reached through two different pathways, both starting in the peripheral nervous system.

Stochastic Model of Supercoiling-Dependent Transcription.

We propose a stochastic model for gene transcription coupled to DNA supercoiling, where we incorporate the experimental observation that polymerases create supercoiling as they unwind the DNA helix and that these enzymes bind more favorably to regions where the genome is unwound. Within this model, we show that when the transcriptionally induced flux of supercoiling increases, there is a sharp crossover from a regime where torsional stresses relax quickly and gene transcription is random, to one where gene expression is highly correlated and tightly regulated by supercoiling. In the latter regime, the model displays transcriptional bursts, waves of supercoiling, and up regulation of divergent or bidirectional genes. It also predicts that topological enzymes which relax twist and writhe should provide a pathway to down regulate transcription.

Gender may be related to the side of the motor syndrome and cognition in idiopathic Parkinson's disease.

BACKGROUND: and Sex and cognitive profile may be related to the laterality of motor symptoms in idiopathic Parkinson's disease. INTRODUCTION: Parkinson's disease (PD) is well recognised as an inherently asymmetric disease with unilateral onset of motor symptoms. The laterality of motor symptoms may be linked to sex, clinical and demographic variables, and neuropsychological disorders. However, the available data are inconsistent. This study aimed to explore the potential association between the laterality of motor symptoms and clinical and demographic variables and deficits in specific cognitive domains. MATERIAL AND METHODS: We retrospectively recruited 97 participants with idiopathic PD without dementia; 60 presented motor symptoms on the left side and 37 on the right side. Both groups were comparable in terms of age, age at disease onset, disease duration, and severity of the neurological deficits according to the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr scale. RESULTS: Participants with left-side motor symptoms scored lower on the Schwab and England Activities of Daily Living scale. Our sample included more men than women (67% vs. 33%). Both sexes were not equally represented in the 2 groups: there were significantly more men than women in the group of patients with left-side motor symptoms (77% vs. 23%), whereas the percentages of men and women in the group of patients with right-side motor symptoms were similar (51% vs. 49%). Both groups performed similarly in all neuropsychological tasks, but women, independently of laterality, performed better than men in the naming task. CONCLUSION: We found a clear prevalence of men in the group of patients with left-side motor symptoms; this group also scored lower on the Schwab and England Scale. Female sex was predictive of better performance in the naming task. Sex should always be considered in disorders that cause asymmetric involvement of the brain, such as PD.

Intrajejunal levodopa infusion in advanced Parkinson's disease: long-term effects on motor and non-motor symptoms and impact on patient's and caregiver's quality of life.

BACKGROUND: Continuous infusion of intrajejunal levodopa/carbidopa gel (CIILG) for advanced Parkinson's disease (PD) has been proved to be beneficial on motor complications, non-motor symptoms and quality of life in the short-term follow-up. Aim of this two-center, retrospective, open-label study was to evaluate the long-term effect of CIILG on patients' condition and caregivers' quality of life. MATERIALS AND METHODS: The assessments (performed at baseline and at latest follow-up available after CIILG) included: the unified PD rating scale (UPDRS I-IV), the non-motor symptoms scale (NMSS), the PD questionnaire (PDQ-8), the PD sleep scale (PDSS), and a battery assessing the cognitive and psychiatric status as well as caregiver's quality of life. Medications were expressed as levodopa equivalent daily dose (LEDD). RESULTS: 14 advanced PD patients (age: 67.0 +/- 11.5 years, disease duration: 12.9 +/- 4.8 years) were followed for 24.9 +/- 14.4 months after CIILG. Total LEDD was unchanged at follow-up, however therapy was globally simplified by reducing dopamine agonists (DAs). A statistically significant beneficial effect was shown on motor complications while the severity of motor symptoms did not change over time. A significant improvement of depressive symptoms and psychiatric side effects caused by DAs was detected. Sleep quality and diurnal somnolence ameliorated as revealed by the significant reduction of PDDS. Caregivers' stress and patients' quality of life were not significantly improved. However, when categorized according to their outcome, patients with improvement of motor condition and functionality gained an improvement of quality of life. Apart from the severity of motor impairment at baseline, no other predicting factors were detected. CONCLUSIONS: CIILG is an effective treatment option for patients with advanced PD over the long-term period as it may improve both the motor complications and the psychiatric side effects caused by other dopaminergic therapies.

Gender may be related to the side of the motor syndrome and cognition in idiopathic Parkinson's disease.

BACKGROUND: and Sex and cognitive profile may be related to the laterality of motor symptoms in idiopathic Parkinson's disease. INTRODUCTION: Parkinson's disease (PD) is well recognised as an inherently asymmetric disease with unilateral onset of motor symptoms. The laterality of motor symptoms may be linked to sex, clinical and demographic variables, and neuropsychological disorders. However, the available data are inconsistent. This study aimed to explore the potential association between the laterality of motor symptoms and clinical and demographic variables and deficits in specific cognitive domains. MATERIAL AND METHODS: We retrospectively recruited 97 participants with idiopathic PD without dementia; 60 presented motor symptoms on the left side and 37 on the right side. Both groups were comparable in terms of age, age at disease onset, disease duration, and severity of the neurological deficits according to the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr scale. RESULTS: Participants with left-side motor symptoms scored lower on the Schwab and England Activities of Daily Living scale. Our sample included more men than women (67% vs. 33%). Both sexes were not equally represented in the 2 groups: there were significantly more men than women in the group of patients with left-side motor symptoms (77% vs. 23%), whereas the percentages of men and women in the group of patients with right-side motor symptoms were similar (51% vs. 49%). Both groups performed similarly in all neuropsychological tasks, but women, independently of laterality, performed better than men in the naming task. CONCLUSION: We found a clear prevalence of men in the group of patients with left-side motor symptoms; this group also scored lower on the Schwab and England Scale. Female sex was predictive of better performance in the naming task. Sex should always be considered in disorders that cause asymmetric involvement of the brain, such as PD.

Lower limb involvement in adult-onset primary dystonia: frequency and clinical features.

BACKGROUND AND PURPOSE: Despite the growing number of reports describing adult-onset primary lower limb dystonia (LLD) this entity has never been systematically evaluated in the general population of patients with primary adult-onset dystonia. METHODS: From outpatients with adult-onset primary dystonia attending nine Italian University centres for movement disorders we consecutively recruited 579 patients to undergo a standardized clinical evaluation. RESULTS: Of the 579 patients assessed, 11 (1.9%) (8 women, 3 men) had LLD, either alone (n = 4, 0.7%) or as part of a segmental/multifocal dystonia (n = 7, 1.2%). The age at onset of LLD (47.9 +/- 17 years) was significantly lower than the age at onset of cranial dystonias (57.9 +/- 10.7 years for blepharospasm, and 58.9 +/- 11.8 years for oromandibular dystonia) but similar to that of all the other adult-onset primary dystonias. The lower limb was either the site of dystonia onset (36.4%) or the site of dystonia spread (63.6%). In patients in whom LLD was a site of spread, dystonia seemed to spread following a somatotopic distribution. Only one patient reported a recent trauma involving the lower limb whereas 36.4% of the patients reported pain at the site of LLD. Only 64% of our patients needed treatment for LLD, and similarly to previously reported cases, the most frequently tried treatments was botulinum toxin and trihexyphenidyl. CONCLUSION: The lower limb is an uncommon but possible topographical site of dystonia in adulthood that should be kept in consideration during clinical evaluation.

Outcome predictors, efficacy and safety of Botox and Dysport in the long-term treatment of hemifacial spasm.

BACKGROUND AND PURPOSE: To review the clinical characteristics and the long-term outcome of patients with hemifacial spasm (HFS) who received botulinum neurotoxin (BoNT) over the past 10 years. RESULTS: A total of 108 patients received 665 treatments. Mean latency of clinical effect was 5.4 +/- 5.3 days for Botox and 4.9 +/- 4.6 days for Dysport (P > 0.05). Mean duration of clinical improvement was higher after the injection of Dysport than Botox: 105.9 +/- 54.2 and 85.4 +/- 41.6 days respectively (P < 0.01). The percentage of treatment failures was 6.5% for Botox and 4.6% for Dysport (P > 0.05). The doses of Botox significantly increased over time (beta = 0.35, P < 0. 001) whilst Dysport dose remained unchanged (beta = 0.16, n.s.). The duration of clinical benefit slightly increased with Botox (beta = 0.12; P < 0.01), but remained constant for Dysport. Side effects occurred in 17.4% of treatments: 16.7% of patients who had received Botox, and in 19.7% who had received Dysport (P > 0.05). The most common side effects were palpebral ptosis and lacrimation; ptosis and lagophtalmos was more common in Dysport treatments (P < 0.005). CONCLUSIONS: Both brands are effective and safe in treating HFS; efficacy is long-lasting. The differences in outcome and side effects confirm that, albeit the active drug is the same, Botox and Dysport should be considered as two different drugs.

Myasthenia gravis: an unrecognized cause of head drop in Parkinson's disease.

Head drop is characterized by marked anterior flexion of the cervical spine, caused by weakness of the neck extensors or by increased tone of the flexor muscles. We report a woman with Parkinson's disease and head drop not due to cervical dystonia (a common cause of antecollis in parkinsonisms). Clinical, radiological, and neurophysiological features together with responsiveness to anticholinesterases and plasma exchanges indicated the possibility of a concomitant myasthenia gravis.

Results by motor cortex stimulation in treatment of focal dystonia, Parkinson's disease and post-ictal spasticity. The experience of the Italian Study Group of the Italian Neurosurgical Society.

Extradural motor cortex stimulation has been employed in cases of Parkinson's disease (PD), fixed dystonia (FD) and spastic hemiparesis (SH) following cerebral stroke. Symptoms of PD are improved by EMCS: results were evaluated on the basis of the UPDRS and statistically analysed. In PD EMCS is less efficacious than bilateral subthalamic nucleus (STN) stimulation, but it may be safely employed in patients not eligible for deep brain stimulation (DBS). The most rewarding effect is the improvement, in severely affected patients, of posture and gait. FD, unresponsive to bilateral pallidal stimulation, has been relieved by EDMS. In SH reduction of spasticiy by EMCS allows improvement of the motor function.

OnabotulinumtoxinA for adductor spasmodic dysphonia (ADSD): Functional results and the role of dosage.

OBJECTIVE: To report the results of functional outcome, dose trend and relationship between onabotulinumtoxinA (onabotA) dosage and the severity of disease or time between therapy sessions in patients affected by adductor spasmodic dysphonia (ADSD). PATIENTS AND METHODS: Thirty-two patients underwent 193 EMG-guided intracordal injections of a starting dose of 2 MU of onabotA. At enrollment, each subject was administered the VHI. The response was evaluated using a subjective rating scale (0-100% of normal phonation). RESULTS: The quality of voice improved significantly after 1 month and stabilized by 3 months. The percentage of normal voice improved 33.34 ±â€¯11.5% (min 26 - max 68). The functional gain was significantly worse in patients presenting with ADSD associated with dystonias in other body regions (31% vs 45% - p < 0.05). The mean dose employed was 3.64 MU (min 1 - max 6) with a trend of increasing dosages up to the 5th treatment after which the doses stabilized over time. The pre-treatment VHI showed a weakly positive correlation with the cumulative dose at the 5th and 10th injections. Benefit duration and the mean between treatment interval were 103 and 136 days respectively. The correlation between dose and inter-injection time is weakly negative (r = -0.22, p < 0.05), however, this is influenced predominantly by the first-to-second injection. After this initial treatment effect, the correlation becomes weakly positive (r = 0.12). CONCLUSIONS: Our data confirm the efficacy of onabotA to improve the quality of voice in cases of ADSD. The trial period for optimal dosage lasted up to a mean of five injections. The dosage of onabotA impacted the length of response and was influenced by the severity of ADSD. Finally the efficacy of onabotA did not change significantly after repeated administrations.

A role for accelerometry in the differential diagnosis of tremor syndromes.

Accelerometry is a reliable tool for gauging the occurrence, amplitude and frequency of tremor. However, there is no consensus on criteria for accelerometric diagnosis of tremor syndromes. We enrolled 20 patients with essential tremor (ET), 20 with dystonic tremor (DT), and 20 with classic parkinsonian tremor (PD-T), all meeting accepted clinical criteria. All the patients underwent dopamine transporter imaging (by means of single-photon emission computed tomography) and triaxial accelerometric tremor analysis. The latter revealed groupwise differences in tremor frequency, peak dispersion, spectral coherence, unilaterality and resting vs action tremor amplitude. From the above, five diagnostic criteria were extrapolated for each condition. Receiver operating characteristic curves, depicting criteriabased scoring of each tremor type, showed negligible declines in specificity for scores ≥4 in patients with ET or DT and scores ≥3 in patients with PD-T, thus providing a simple scoring method (accelerometrically derived) for differential diagnosis of the principal tremor syndromes.

Gender may be related to the side of the motor syndrome and cognition in idiopathic Parkinson's disease / Posible relación entre sexo y perfil cognitivo y la lateralidad de los síntomas motores en la enfermedad de Parkinson idiopática

Background: and Sex and cognitive profile may be related to the laterality of motor symptoms in idiopathic Parkinson's disease. Introduction: Parkinson's disease (PD) is well recognised as an inherently asymmetric disease with unilateral onset of motor symptoms. The laterality of motor symptoms may be linked to sex, clinical and demographic variables, and neuropsychological disorders. However, the available data are inconsistent. This study aimed to explore the potential association between the laterality of motor symptoms and clinical and demographic variables and deficits in specific cognitive domains. Material and methods: We retrospectively recruited 97 participants with idiopathic PD without dementia; 60 presented motor symptoms on the left side and 37 on the right side. Both groups were comparable in terms of age, age at disease onset, disease duration, and severity of the neurological deficits according to the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr scale. Results: Participants with left-side motor symptoms scored lower on the Schwab and England Activities of Daily Living scale. Our sample included more men than women (67% vs. 33%). Both sexes were not equally represented in the 2 groups: there were significantly more men than women in the group of patients with left-side motor symptoms (77% vs. 23%), whereas the percentages of men and women in the group of patients with right-side motor symptoms were similar (51% vs. 49%). Both groups performed similarly in all neuropsychological tasks, but women, independently of laterality, performed better than men in the naming task. Conclusion: We found a clear prevalence of men in the group of patients with left-side motor symptoms; this group also scored lower on the Schwab and England Scale. Female sex was predictive of better performance in the naming task. Sex should always be considered in disorders that cause asymmetric involvement of the brain, such as PD.(AU)

Introducción: La enfermedad de Parkinson (EP) es una enfermedad asimétrica en la que los primeros síntomas se presentan solo en un lado del cuerpo. El lado de inicio de la sintomatología puede depender del sexo, de variables clínicas y demográficas y de la presencia de trastornos neuropsicológicos. Sin embargo, la evidencia disponible no es consistente. Nuestro estudio pretende determinar si el lado que presenta síntomas motores tiene alguna relación con variables clínicas y demográficas y con déficits en determinados dominios cognitivos. Materiales y métodos: Incluimos 97 individuos con EP y sin demencia; 60 de ellos tenían síntomas motores en el lado izquierdo y 37 en el lado derecho. Ambos grupos presentaban similitudes en cuanto a edad, edad de inicio de la enfermedad, duración de la enfermedad, y gravedad de los síntomas neurológicos, según la Unified Parkinson's Disease Rating Scale y la Hoehn and Yahr Scale. Resultados: Los participantes con síntomas en el lado izquierdo obtuvieron puntuaciones más bajas en la Escala de Actividades de la Vida Diaria de Schwab y England. Nuestra muestra incluía más hombres que mujeres (67 vs. 33%). Además, la distribución de hombres y mujeres no era equitativa entre los dos grupos; había un número significativamente mayor de hombres en el grupo de pacientes con síntomas en el lado izquierdo (77 vs. 23%), mientras que la distribución por sexo era similar en el grupo de pacientes con síntomas en el lado derecho (51 vs. 49%). No encontramos diferencias en las puntuaciones de ninguna de las pruebas neuropsicológicas entre los grupos. Sin embargo, las mujeres, independientemente del lado afecto, obtuvieron mejores resultados que los hombres en la prueba de denominación. Conclusiones: Los hombres eran mucho más numerosos en el grupo de pacientes con afectación del lado izquierdo; este grupo mostró peores puntuaciones en la escala de Schwab y England...(AU)