Does sex influence the natural history of idiopathic adult-onset dystonia?

BACKGROUND: Several earlier studies showed a female predominance in idiopathic adult-onset dystonia (IAOD) affecting the craniocervical area and a male preponderance in limb dystonia. However, sex-related differences may result from bias inherent to study design. Moreover, information is lacking on whether sex-related differences exist in expressing other dystonia-associated features and dystonia spread. OBJECTIVE: To provide accurate information on the relationship between sex differences, motor phenomenology, dystonia-associated features and the natural history of IAOD. METHODS: Data of 1701 patients with IAOD from the Italian Dystonia Registry were analysed. RESULTS: Women predominated over men in blepharospasm, oromandibular, laryngeal and cervical dystonia; the sex ratio was reversed in task-specific upper limb dystonia; and no clear sex difference emerged in non-task-specific upper limb dystonia and lower limb dystonia. This pattern was present at disease onset and the last examination. Women and men did not significantly differ for several dystonia-associated features and tendency to spread. In women and men, the absolute number of individuals who developed dystonia tended to increase from 20 to 60 years and then declined. However, when we stratified by site of dystonia onset, different patterns of female-to-male ratio over time could be observed in the various forms of dystonia. CONCLUSIONS: Our findings provide novel evidence on sex as a key mediator of IAOD phenotype at disease onset. Age-related sexual dimorphism may result from the varying exposures to specific age-related and sex-related environmental risk factors interacting in a complex manner with biological factors such as hormonal sex factors.

Does thyroid diseases contribute to the natural history of idiopathic adult-onset dystonia? Data from the Italian Dystonia Registry.

A few earlier observations and recent controlled studies pointed to the possible contribution of thyroid diseases in idiopathic adult-onset dystonia (IAOD). The aim of this study was to investigate the association between thyroid status and clinical characteristics of IAOD, focusing on dystonia localization, spread, and associated features such as tremors and sensory tricks. Patients were identified from those included in the Italian Dystonia Registry, a multicentre dataset of patients with adult-onset dystonia. The study population included 1518 IAOD patients. Patients with hypothyroidism and hyperthyroidism were compared with those without any thyroid disease. In the 1518 IAOD patients, 167 patients (11%; 95% CI 9.5-12.6%) were diagnosed with hypothyroidism and 42 (2.8%; 95% CI 1.99-3.74) with hyperthyroidism. The three groups were comparable in age at dystonia onset, but there were more women than men in the groups with thyroid disease. Analysing the anatomical distribution of dystonia, more patients with blepharospasm were present in the hyperthyroidism group, but the difference did not reach statistical significance after the Bonferroni correction. The remaining dystonia-affected body sites were similarly distributed in the three groups, as did dystonia-associated features and spread. Our findings provided novel information indicating that the high rate of thyroid diseases is not specific for any specific dystonia subpopulation and does not appear to influence the natural history of the disease.

Oromandibular dystonia: from onset to spread a multicenter italian study.

BACKGROUND: Detailed information about the epidemiological and phenomenological differences among the aetiological subtypes of oromandibular dystonia (OMD) is lacking. Moreover, the OMD tendency to spread to other body sites has never been investigated. AIM: To compare the main demographic and clinical features of OMD in different aetiological groups and assess the risk of spread. MATERIALS AND METHODS: We retrospectively analysed data from patients contained in the Italian Dystonia Registry. The risk of spread was assessed by Kaplan Meyer curves and Cox regression analysis. RESULTS: The study included 273 patients (175 women) aged 55.7 years (SD 12.7) at OMD onset. Female predominance was observed. Idiopathic dystonia was diagnosed in 241 patients, acquired dystonia in 22. In 50/273 patients, dystonia started in the oromandibular region (focal OMD onset); in 96/273 patients the onset involved the oromandibular region and a neighbouring body site (segmental/multifocal OMD onset); and in 127/273 patients OMD was a site of spread from another body region. Sensory trick (ST) and positive family history predominated in the idiopathic group. No dystonia spread was detected in the acquired group, whereas spread mostly occurred within the first five years of history in 34% of the focal OMD onset idiopathic patients. Cox regression analysis revealed ST as a significant predictor of spread (HR, 12.1; 95% CI, 2.5 - 18.8; P = 0.002). CONCLUSION: This large study provides novel information about the clinical phenomenology of idiopathic and acquired OMD. We pointed out a possible role of oestrogens in favouring dystonia development. Moreover, we described for the first time the association between ST and dystonia spread, revealing possible common pathophysiological mechanisms. Our findings may be suggested as a referral point for future pathophysiological and therapeutic studies on OMD.

2:1 ketogenic diet and low-glycemic-index diet for the treatment of chronic and episodic migraine: a single-center real-life retrospective study.

AIMS: The evidence supporting the efficacy of dietary preventive therapy in migraine is rising, particularly regarding the ketogenic diet. However, less evidence exists for the Low-Glycemic Index Diet and the 2:1 KD. This retrospective single-center real-life study aims to evaluate the efficacy of a 2:1 ketogenic diet and a Low-Glycemic-index Diet in chronic and high-frequency episodic migraine. METHODS: Sixty patients with high-frequency episodic and chronic migraine were treated with either a Low-Glycemic-index diet (39 patients) or a 2:1 (21 patients) ketogenic diet for three months. We collected data on the migraine frequency and intensity and the MIDAS and HIT-6 scores through the headache diary. Anthropometric measurements (BMI, fat mass, free fat mass, and weight) were also collected and analyzed similarly. Data obtained at the baseline and after three months of each diet were compared. RESULTS: Migraine intensity, frequency, MIDAS and HIT-6 scores, fat mass, weight, and BMI improved in both diet groups. CONCLUSIONS: Both diets are effective in reducing migraine symptoms and migraine-related disability.

Performing real time neuropsychological testing during awake craniotomy: are dexmedetomidine or propofol the same? A preliminary report.

PURPOSE: In awake surgery, the patient is sedated, but is also required to be sufficiently alert and collaborative during extensive neurocognitive testing. In the present preliminary report of a retrospective single-center study, a continuous series of 168 patients who underwent awake surgery for brain tumor located near eloquent areas, was investigated to observe the effect of dexmedetomidine (n = 58) compared with propofol (n = 110) on vigilance and collaboration required to perform extensive intra-operatory Real Time Neuropsychological Testing (RTNT). METHODS: We assigned a score to each patient, by using a scale that combines vigilance and collaboration in a 5 levels score (the higher score denoting higher level). RESULTS: The median interquartile range was significantly lower (range 3-5) for the dexmedetomidine group compared to the propofol one (range 4-5, p = .044). Patients with intra-operative seizures (p = .014) and/or electrocorticographic slow/epileptiform activity (p = .042), and patients in the propofol group who showed increased heart rate (p = .032) were those who obtained the lower scores (lower vigilance and collaboration level). CONCLUSION: The study shows that the effect of dexmedetomidine or propofol -based conscious sedation on ability to perform Real Time Neuropsychological Testing during awake surgery for supratentorial tumor resection is different. Although both permit high mean levels of vigilance and collaboration, the patient who received dexmedetomidine was more likely to show lower vigilance and collaboration during RTNT.

Clinical and neurophysiological characterization of muscular weakness in severe COVID-19.

OBJECTIVE: To report clinical and electroneuromyographic (ENMG) characteristics of patients affected by severe COVID-19 infection, evaluated for muscular weakness. MATERIALS AND METHODS: ENMGs performed for evaluation of diffuse weakness in patients who could not be discharged from semi-intensive care COVID unit because of difficulties in ventilation weaning were reviewed. Patients with severe COVID-19 infection who had undergone endotracheal intubation and able to co-operate were considered. ENMG protocol was focused on neurophysiological items that excluded or confirmed critical illness polyneuropathy (CIP), myopathy (CIM), or polyneuromyopathy (CIPM). Standardized clinical evaluation was performed using Medical Research Council (MRC) sum score. RESULTS: Eight patients were included in the study. All presented known risk factors for intensive care unit-acquired weakness (ICU-AW), and none of them had history of underlying neuromuscular disorders. ENMG findings were normal in two patients, while only two patients had an altered MRC sum score (< 48). Neuromuscular involvement was diagnosed in 6/8 patients (75%): 2 had CIP, 1 had possible CIM, 1 had CIPM, while 1 patient, with clinically evident weakness but equivocal ENMG findings, was classified as ICU-AW. Finally, 1 patient was diagnosed with acute demyelinating neuropathy. Patients with neuromuscular involvement were those with longer intubation duration and higher levels of IL-6 at admission. CONCLUSION: Neuromuscular complications are frequent in severe COVID-19 and cannot be excluded by MRC sum scores above 48. Standardized ENMG is helpful in guiding diagnosis when clinical evaluation is not reliable or possible. Elevated IL-6 at admission may be a predictor biomarker of ICU-AW in COVID-19.

Frameless Deep Brain Stimulation Surgery: A Single-Center Experience and Retrospective Analysis of Placement Accuracy of 220 Electrodes in a Series of 110 Patients.

BACKGROUND: Proper lead placement is considered one of the key factors in achieving a good clinical outcome in deep brain stimulation (DBS), but there is still considerable controversy surrounding the accuracy of the frameless in comparison to the frame-based technique. OBJECTIVE: We report our single-center experience with DBS electrode placement to evaluate the accuracy of the frameless stereotactic system. METHODS: We prospectively analyzed the data of 110 patients who underwent DBS surgery for Parkinson disease, dystonia, essential tremor, or refractory epilepsy. The final targets (FTs) of the 220 leads were: subthalamic nucleus, globus pallidus pars interna, ventralis intermedius nucleus, and anterior nuclei of thalamus in thalamus. A bilateral stereotactic approach using a combined identification of target based on preoperative images (MRI and CT scan fusion) and intra-operative micro-electrode recording (MER) were done. We collected and compared the coordinates of planned target (PT), the definitive expected target (ET) during MER, and the effective final location (FT) of the lead using the postoperative CT. Accuracy was assessed by both vector error (VE) and deviation from the PT. RESULTS: The mean and SD from PTs was 0.78 ± 0.43 mm in the x direction, 0.68 ± 0.41 mm in the y direction, and 0.76 ± 0.41 mm in the z direction. Global VE was 1.43 ± 0.37. CONCLUSION: Frameless systems appear to be a reliable and accurate technique.

Levodopa/carbidopa intestinal gel therapy for advanced Parkinson Disease: AN early toxic effect for small nerve fibers?

INTRODUCTION: Peripheral neuropathy related to levodopa/carbidopa intestinal gel (LCIG) therapy for advanced Parkinson disease (PD) is under investigation and is debated in the literature. The purpose of the study was to detect whether small nerve fibers are damaged during LCIG infusion. METHODS: Five advanced PD patients were enrolled prior to starting LCIG infusion. Six PD patients on oral levodopa (LD) treatment and 6 PD patients naïve to LD were also enrolled. Clinical examination, the Quantitative Sensory Testing battery testing, nerve conduction studies, and intraepidermal nerve fiber density examinations were collected at baseline and at 3, 6, and 12 months after LCIG infusion was started in the study cohort. RESULTS: After 3, 6, and 12 months, severe skin denervation and increased thermal thresholds were observed in the LCIG group. CONCLUSIONS: Significant damage to small nerve fibers was detected in PD patients soon after LCIG infusion had started, suggesting careful monitoring of small fiber impairment during LCIG is needed. Muscle Nerve, 2016 Muscle Nerve 54: 970-972, 2016.

Chronic post-traumatic neuropathic pain of brachial plexus and upper limb: a new technique of peripheral nerve stimulation.

The aim of the study was to evaluate the effect on pain relief in patients with peripheral neuropathic pain after brachial plexus injuries using an implanted peripheral nerve stimulator applied directly to the nerve branch involved into the axillary cavity. Seven patients with post-traumatic brachial plexus lesions or distal peripheral nerve complaining of severe intractable chronic pain were enrolled in a single-centre, open-label trial. Conventional drugs and traditional surgical treatment were not effective. Patients underwent careful neurological evaluation, pain questionnaires and quantitative sensory testing (QST). Surgical treatment consists of a new surgical technique: a quadripolar electrode lead was placed directly on the sensory peripheral branch of the main nerve involved, proximally to the site of lesion, into the axillary cavity. To assess the effect, we performed a complete neuroalgological evaluation and QST battery after 1 week and again after 1, 6 and 12 weeks. All patients at baseline experienced severe pain with severe positive phenomena in the median (5) and/or radial (2) territory. After turning on the neuro-stimulator system, all patients experienced pain relief within a few minutes (>75 % and >95 % in most), with long-lasting pain relief with a reduction in mean Numerical Rating Scale (NRS) of 76.2 % after 6 months and of 71.5 % after 12 months. No significant adverse events occurred. We recommend and encourage this surgical technique for safety reasons; complications such as dislocation of electrocatheters are avoided. The peripheral nerve stimulation is effective and in severe neuropathic pain after post-traumatic nerve injuries of the upper limbs.

Pulsed Radiofrequency for Auriculotemporal Neuralgia: A Case Report.

Auriculotemporal neuralgia is a rare facial pain disorder with no therapeutic evidence for refractory cases. We described a male patient with right auriculotemporal neuralgia, refractory to anesthetic nerve blocks and botulinum toxin type A injections, who was successfully treated with pulsed radiofrequency without adverse events. Pulsed radiofrequency may be an effective and safe treatment for refractory auriculotemporal neuralgia.

Botulinum Toxin Type A for the Treatment of Auriculotemporal Neuralgia-A Case Series.

Auriculotemporal neuralgia is a rare pain disorder in which anesthetic nerve blockade is usually effective but not always resolutive. Botulinum toxin type A has proven to be effective in treating neuropathic pain, and patients with auriculotemporal neuralgia could also benefit from this treatment. We described nine patients with auriculotemporal neuralgia treated with botulinum toxin type A in the territory of auriculotemporal nerve innervation. We compared the basal NRS and Penn facial pain scale scores with those obtained 1 month after BoNT/A injections. Both Penn facial pain scale (96.67 ± 24.61 vs. 45.11 ± 36.70, p 0.004; mean reduction 52.57 ± 36.50) and NRS scores (8.11 ± 1.27 vs. 4.22 ± 2.95, p 0.009; mean reduction 3.89 ± 2.52) improved significantly at one month after treatment. The mean duration of the effect of BoNT/A on pain was 95.00 ± 53.03 days and no adverse effects were reported.

Limits and usefulness of intraoperative evoked potentials during laminoplasty.

BACKGROUND: Over the past 10 years, intraoperative neurophysiological monitoring (IONM) has been widely performed during surgery for treating spondylotic cervical myelopathy. Our study considers the predictive value of IONM during laminoplasty, regarding, first, the adequacy of spinal cord decompression and, second, the long-term neuro-functional outcome. METHODS: We considered 38 patients with the diagnosis of degenerative cervical myelopathy who underwent an open-door laminoplasty. All patients were evaluated preoperatively, and at three and 12 months postoperatively, with the Japanese Orthopedic Association (JOA) point scale. Upper and lower limb somatosensory and motor evoked potentials (SSEPs and MEPs) were recorded preoperatively and intraoperatively. RESULTS: During surgery, three of 38 patients showed a deterioration of SSEPs and MEPs compared to baseline values. Surgery was then converted from laminoplasty to laminectomy, resulting in the gradual restoration of the evoked potentials. The neurophysiological parameter significantly associated with a better clinical outcome was the latency of lower limbs MEPs. The 12 patients who had a more prominent reduction of the MEPs latency at the end of surgery showed a higher post-surgical JOA score, increasing ≥30% compared to baseline values at the 3- and 12-month follow-up. CONCLUSIONS: Though not a predictor of clinical outcome, the IONM was essential to evaluate the effectiveness of spinal cord decompression. Reduced latency of lower limbs MEPs may predict a better clinical outcome. We suggest that IONM in patients with degenerative cervical myelopathy should be routine. It is necessary to conduct larger studies to clarify the predictive value of IONM.

Dystonic tremor and blepharospasm in a patient with deletion of 18q.

18q- Syndrome is a rare chromosomic syndrome where neurological involvement is scarcely described. Movement disorders are rare and only one case with dystonia was described. In our paper, we describe the second report of a patient with 18q- Syndrome, blepharospasm, and dystonic tremor of his right hand and hyperthyroidism instead of hypothyroidism.

Botulinum toxin type a for great auricular neuralgia.

great auricular neuralgia is a rare disorder with only 18 cases described in the literature. Since it's a rare disorder, there are no evidence-based therapeutic recommendations but only case reports to guide physicians. We report a case of great auricular neuralgia treated with botulinum toxin type A subcutaneous injection with significant remission of pain. Botulinum toxin type A could be an effective and safe treatment in this setting; however, more studies are needed to confirm our results.

Efficacy and safety of two different botulinum toxin type A dilutions in chronic migraineurs.

Botulinum toxin type A is an effective preventive therapy for chronic migraine. Although the guidelines suggest a 50U/ml dilution of OnabotulinumtoxinA (BoNT/A), many clinicians use more concentrated solutions. However, there are no studies regarding the effect and safety of 100U/ml BoNT/A dilution with the saline solution following the PREEMPT paradigm. Our primary goal was to evaluate the efficacy, in reducing migraine frequency, and safety of two different BoNT/A dilutions (100U/ml vs 50U/ml) in the treatment of Chronic migraine. Our secondary goal was to determine the predictors of BoNT/A response. We retrospectively collected data from 113 chronic migraine patients treated with 3 rounds of BoNT/A according to the PREEMPT protocol as a preventive therapy. Patients were divided into two groups, based on BoNT/A dilution: 50U/ml (49 patients) vs. 100U/ml (64 patients) of sodium chloride 0.9%. We compared the migraine days/month, intensity, and intake of symptomatic medications at the baseline with the data obtained after the treatment; moreover, we evaluated the occurrence of adverse effects observed in the two groups. There was no difference regarding efficacy and safety between the two groups except for eyelid ptosis, which was more common in the 50U/ml BoNT/A group (p 0.018). Unilateral localization of migraine was associated with a more favorable outcome (OR 5.593, C.I. 2.358-13.268; p < 0.001) while Major Depressive Disorder predicted a less favorable response (OR 0.213, C.I. 0.087-0.523; p < 0.001). In our study, BoNT/A dilution did not influence the response to the therapy, but 100U/ml dilution could reduce the risk of eyelid ptosis. Unilateral localization of migraine pain might predict a more favorable response to the therapy, while the presence of a Major Depressive Disorder might predict a less favorable response.

Nummular headache: a case report of remission following ketogenic diet and botulinum toxin type A injections.

Nummular headache is an unusual facial pain disorder with no evidence-based therapy recommendations. The ketogenic diet is an alternative therapy that demonstrated to be effective in migraineurs, but it was never used in the setting of nummular headache. We describe a 58-years old female patient with nummular headache successfully treated with a 6-months ketogenic diet and botulinum toxin type A injections. Ketogenic diet could be an effective alternative/complementary therapy in nummular headache patients although more studies are needed to confirm our results.

Efficacy of Perampanel in Refractory and Super-Refractory Status Epilepticus with Suspected Inflammatory Etiology: A Case Series.

(1) Background: Increasing evidence supports the anti-inflammatory and neuroprotective role of perampanel (PER), mediated by decreased expression of pro-inflammatory cytokines and by interference with apoptosis processes. Therefore, the use of PER to treat status epilepticus (SE) with suspected inflammatory etiology is appealing and deserves further investigation. (2) Methods: We retrospectively analyzed seven patients (five F, two M; median age: 62 years) with refractory and super-refractory SE due to a probable or defined inflammatory etiology and treated with PER. (3) Results: PER was administered as the third (4/7) or fourth drug (3/7), with a median loading dose of 32 mg/day (range: 16-36 mg/day) and a median maintenance dose of 10 mg/day (range: 4-12 mg/day). In five cases, SE was focal, while in two patients, it was generalized. SE was caused by systemic inflammation in three patients, while in the other four subjects, it was recognized to have an autoimmune etiology. SE resolution was observed after PER administration in all cases, particularly within 24 h in the majority of patients (4/7, 57.1%). (4) Conclusions: Our data support the efficacy of PER in treating SE when first- and second-line ASMs have failed and suggest a possible earlier use in SE cases that are due to inflammatory/autoimmune etiology.

Risk Factors for Intraoperative Seizures in Glioma Surgery: Electrocorticography Matters.

PURPOSE: Few and contradictory data are available regarding intraoperative seizures during surgery for low-grade gliomas. Aim of this study was to evaluate possible risk factors for the occurrence of IOS. METHODS: The authors performed a retrospective analysis of 155 patients affected by low-grade gliomas and tumor-related epilepsy, who underwent surgery in our Department, between 2007 and 2018. A statistical analysis was performed by means of univariate and multivariate regression to evaluate any possible correlation between seizure occurrence and several demographic, clinical, neurophysiological, and histopathological features. RESULTS: Intraoperative seizure occurred in 39 patients (25.16%) with a total of 62 seizure events recorded. Focal seizures were the prevalent seizure type: among them, 39 seizures did not show motor signs, being those with only electrographic and/or with cognitive features the most represented subtypes. Twenty-six seizures occurring during surgery were not spontaneous: direct cortical stimulation with Penfield paradigm was the most prevalent evoking factor. The univariate analysis showed that the following prognostic factors were statistically associated with the occurrence of intraoperative seizure: the awake technique ( P = 0.01) and the interictal epileptiform discharges detected on the baseline electrocorticography (ECoG) ( P < 0.001). After controlling for confounding factors with multivariate analysis, the awake surgery and the epileptic ECoG pattern kept statistical significance. CONCLUSIONS: The awake surgery procedure and the epileptic ECoG pattern are risk factors for intraoperative seizure. ECoG is mandatory to detect electrographic seizures or seizures without motor signs.

Fast or Slow? A Comparison Between Two Transcranial Electrical Stimulation Techniques for Eliciting Motor-Evoked Potentials During Supratentorial Surgery.

PURPOSE: During intraoperative neurophysiological monitoring of motor pathways, two types of transcranial electrical stimulation are available, i.e., constant-current and constant-voltage stimulation. Few previous studies, performed only during spinal surgery, analyzed and compared them during intraoperative neurophysiological monitoring. The aim of our study was to compare these two stimulation techniques for eliciting motor-evoked potentials during intraoperative neurophysiological monitoring in a group of patients affected by supratentorial lesions. METHODS: Supratentorial lesions from 16 patients were retrospectively collected and analyzed. Motor-evoked potentials were performed only from transcranial electrical stimulation because the inability to place the subdural strip electrodes correctly did not permit to perform direct cortical stimulation. At the beginning of surgery, in each patient, motor-evoked potentials were monitored by using both "fast-charge" constant-voltage and "slow-charge" constant-current stimulation. Several neurophysiological parameters were collected and compared between the two stimulation techniques by means of statistical analysis. RESULTS: "Fast-charge" constant-voltage stimulation allowed statistically higher efficiency rates for eliciting motor-evoked potentials compared with "slow-charge" constant-current stimulation, both for upper and lower limbs. We also found that threshold and maximal charge as well as charge density were significantly lower during constant-voltage stimulation, thus lowering the potential tissue damage. CONCLUSIONS: "Fast-charge" constant-voltage transcranial electrical stimulation is feasible and safe during intraoperative neurophysiological monitoring for supratentorial surgery and may be preferable to "slow-charge" constant-current stimulation.