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.

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.

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.

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.

Cognitive outcome 5 years after bilateral chronic stimulation of subthalamic nucleus in patients with Parkinson's disease.

AIM: To assess the long-term cognitive and behavioural outcome after bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients affected by Parkinson's disease, with a 5-year follow-up after surgery. METHODS: 11 patients with Parkinson's disease treated by bilateral DBS of STN underwent cognitive and behavioural assessments before implantation, and 1 and 5 years after surgery. Postoperative cognitive assessments were carried out with stimulators turned on. RESULTS: A year after surgery, there was a marginally significant decline on a letter verbal fluency task (p = 0.045) and a significant improvement on Mini-Mental State Examination (p = 0.009). 5 years after surgery, a significant decline was observed on a letter verbal fluency task (p = 0.007) and an abstract reasoning task (p = 0.009), namely Raven's Progressive Matrices 1947. No significant postoperative change was observed on other cognitive variables. No patient developed dementia 5 years after surgery. A few days after the implantation, two patients developed transient manic symptoms with hypersexuality and one patient developed persistent apathy. CONCLUSION: The decline of verbal fluency observed 5 years after implantation for DBS in STN did not have a clinically meaningful effect on daily living activities in our patients with Parkinson's disease. As no patient developed global cognitive deterioration in our sample, these findings suggest that DBS of STN is associated with a low cognitive and behavioural morbidity over a 5-year follow-up, when selection criteria for neurosurgery are strict.

Long-Term Abobotulinumtoxin A Treatment of Cervical Dystonia.

Botulinum toxin is considered as first-line therapy for cervical dystonia, but few papers have addressed these issues in the long term. Aim of this study was to investigate the long-term efficacy and safety of abobotulinumtoxin A (A/Abo) in patients with primary cervical dystonia. Consecutive patients who received at least six injections with A/Abo were included. Safety was assessed on patients' self-reports. Efficacy was assessed by recording the total duration of benefit, duration of maximum efficacy, disease severity measured by means of the Tsui score, and pain intensity evaluated by means of the visual analog scale (VAS). Thirty-nine patients with PCD were included. The mean dose injected was 701.5 ± 280.6 U. The mean duration of the clinical improvement was 93.0 ± 30.7 days, while the mean duration of the maximum clinical improvement was 77.1 ± 27.1 days. The mean VAS before and 4 weeks after injection was 4.4 ± 1.8 and 1.8 ± 1.6, respectively. The mean Tsui score before and 4 weeks after treatment was 5.7 ± 1.8 and 3.5 ± 1.5, respectively. Doses of A/Abo and duration of the maximum clinical improvement significantly increased over time, while the Tsui score and VAS displayed a tendency to decrease along time. Side effects occurred in 19.6% of all the treatments but were severe in only four injections. The results of our study confirm the effectiveness and safety profile of A/Abo for the long-term treatment of primary cervical dystonia.

Onset and progression of primary torsion dystonia in sporadic and familial cases.

Four hundred and sixty records of patients with primary torsion dystonia (296 women and 164 men) were evaluated. The mean age at disease onset was 48.3 +/- 17.7 years; 13 patients carried the DYT1 CAG deletion. The distribution of age at onset was represented by a bi-modal curve, with a nadir at 21 year separating early onset from late onset cases. In 15.9% of cases there was a positive family history of dystonia. Cranial, cervical or lower limb onset was more common amongst women (M:F ratios were 1:2.7, 1:1.9, and 1:3); by contrast, onset in the upper limb was more common in men (M:F ratio 2.2:1). As expected, disease progression was more pronounced in cases with early onset; it was reckoned that onset at or above 32 years was associated with a negligible likelihood to progress to a generalized form. The mean age at onset of familial cases was 44.8 +/- 11.2 years, significantly lower than the mean age at onset of sporadic cases (53.5 +/- 13.4 years). Familial cases were characterized by more sites involved throughout disease course. Familial cases had a higher tendency to progress to a segmental or generalized form than sporadic cases.