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Contains fulltext : 252096.pdf (Publisher’s version ) (Open Access) In 2016, the Movement Disorder Society Task Force for the Nomenclature of Genetic Movement Disorders presented a new system for naming genetically determined movement disorders and provided a criterion-based list of confirmed monogenic movement disorders. Since then, a substantial number of novel disease-causing genes have been described, which warrant classification using this system. In addition, with this update, we further refined the system and propose dissolving the imaging-based categories of Primary Familial Brain Calcification and Neurodegeneration with Brain Iron Accumulation and reclassifying these genetic conditions according to their predominant phenotype. We also introduce the novel category of Mixed Movement Disorders (MxMD), which includes conditions linked to multiple equally prominent movement disorder phenotypes. In this article, we present updated lists of newly confirmed monogenic causes of movement disorders. We found a total of 89 different newly identified genes that warrant a prefix based on our criteria; 6 genes for parkinsonism, 21 for dystonia, 38 for dominant and recessive ataxia, 5 for chorea, 7 for myoclonus, 13 for spastic paraplegia, 3 for paroxysmal movement disorders, and 6 for mixed movement disorder phenotypes; 10 genes were linked to combined phenotypes and have been assigned two new prefixes. The updated lists represent a resource for clinicians and researchers alike and they have also been published on the website of the Task Force for the Nomenclature of Genetic Movement Disorders on the homepage of the International Parkinson and Movement Disorder Society (https://www.movementdisorders.org/MDS/About/Committees--Other-Groups/MDS-Task-Forces/Task-Force-on-Nomenclature-in-Movement-Disorders.htm). © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Background Systemic lupus erythematosus (SLE) is regarded as a prototype autoimmune disease because it can serve as a means for studying differences between ethnic minorities and sex. Traditionally, all Hispanics have been bracketed within the same ethnic group, but there are differences between Hispanics from Spain and those from Latin America, not to mention other Spanish-speaking populations. Objectives This study aimed to determine the demographic and clinical characteristics, severity, activity, damage, mortality and co-morbidity of SLE in Hispanics belonging to the two ethnic groups resident in Spain, and to identify any differences. Methods This was an observational, multi-centre, retrospective study. The demographic and clinical variables of patients with SLE from 45 rheumatology units were collected. The study was conducted in accordance with Good Clinical Practice guidelines. Hispanic patients from the registry were divided into two groups: Spaniards or European Caucasians (EC) and Latin American mestizos (LAM). Comparative univariate and multivariate statistical analyses were carried out. Results A total of 3490 SLE patients were included, 90% of whom were female; 3305 (92%) EC and 185 (5%) LAM. LAM patients experienced their first lupus symptoms four years earlier than EC patients and were diagnosed and included in the registry younger, and their SLE was of a shorter duration. The time in months from the first SLE symptoms to diagnosis was longer in EC patients, as were the follow-up periods. LAM patients exhibited higher prevalence rates of myositis, haemolytic anaemia and nephritis, but there were no differences in histological type or serositis. Anti-Sm, anti-Ro and anti-RNP antibodies were more frequently found in LAM patients. LAM patients also had higher levels of disease activity, severity and hospital admissions. However, there were no differences in damage index, mortality or co-morbidity index. In the multivariate analysis, after adjusting for confounders, in several models the odds ratio (95% confidence interval) for a Katz severity index >3 in LAM patients was 1.45 (1.038–2.026; p = 0.02). This difference did not extend to activity levels (i.e. SLEDAI >3; 0.98 (0.30–1.66)). Conclusion SLE in Hispanic EC patients showed clinical differences compared to Hispanic LAM patients. The latter more frequently suffered nephritis and higher severity indices. This study shows that where lupus is concerned, not all Hispanics are equal.

OBJECTIVE: To profile European trends in pediatric epilepsy surgery (

Objectives: To identify patterns (clusters) of damage manifestation within a large cohort of juvenile SLE (jSLE) patients and evaluate their possible association with mortality. Methods: This is a multicentre, descriptive, cross-sectional study of a cohort of 345 jSLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestation were identified and compared. Results: Mean age (years) ± S.D. at diagnosis was 14.2 ± 2.89; 88.7% were female and 93.4% were Caucasian. Mean SLICC/ACR DI ± S.D. was 1.27 ± 1.63. A total of 12 (3.5%) patients died. Three damage clusters were identified: Cluster 1 (72.7% of patients) presented a lower number of individuals with damage (22.3% vs. 100% in Clusters 2 and 3, P < 0.001); Cluster 2 (14.5% of patients) was characterized by renal damage in 60% of patients, significantly more than Clusters 1 and 3 (P < 0.001), in addition to increased more ocular, cardiovascular and gonadal damage; Cluster 3 (12.7%) was the only group with musculoskeletal damage (100%), significantly higher than in Clusters 1 and 2 (P < 0.001). The overall mortality rate in Cluster 2 was 2.2 times higher than that in Cluster 3 and 5 times higher than that in Cluster 1 (P < 0.017 for both comparisons). Conclusions: In a large cohort of jSLE patients, renal and musculoskeletal damage manifestations were the two dominant forms of damage by which patients were sorted into clinically meaningful clusters. We found two clusters of jSLE with important clinical damage that were associated with higher rates of mortality, especially for the cluster of patients with predominant renal damage. Physicians should be particularly vigilant to the early prevention of damage in this subset of jSLE patients with kidney involvement.

Background The International Parkinson and Movement Disorders Society criteria for mild cognitive impairment in Parkinson’s disease were recently formulated. Objectives The aim of this international study was to evaluate the predictive validity of the comprehensive (level II) version of these criteria by assessment of their contribution to the hazard of Parkinson’s disease dementia. Methods Individual patient data were selected from four separate studies on cognition in Parkinson’s disease that provided information on demographics, motor examination, depression, neuropsychological examination suitable for application of level II criteria, and longitudinal follow-up for conversion to dementia. Survival analysis evaluated the predictive value of level II criteria for cognitive decline towards dementia as expressed by the relative hazard of dementia. Results A total of 467 patients were included. The analyses showed a clear contribution of impairment according to level II mild cognitive impairment criteria, age and severity of Parkinson’s disease motor symptoms to the hazard of dementia. There was a trend of increasing hazard of dementia with declining neuropsychological performance. Conclusions This is the first large international study evaluating the predictive validity of level II mild cognitive impairment criteria for Parkinson’s disease. The results showed a clear and unique contribution of classification according to level II criteria to the hazard of Parkinson’s disease dementia. This finding supports their predictive validity and shows that they contribute important new information on the hazard of dementia, beyond known demographic and Parkinson’s disease specific factors of influence., Michael J. Fox Foundation Dutch Parkinson Foundation

This article reviews and summarizes 200 years of Parkinson's disease. It comprises a relevant history of Dr. James Parkinson's himself and what he described accurately and what he missed from today's perspective. Parkinson's disease today is understood as a multietiological condition with uncertain etiopathogenesis. Many advances have occurred regarding pathophysiology and symptomatic treatments, but critically important issues are still pending resolution. Among the latter, the need to modify disease progression is undoubtedly a priority. In sum, this multiple-author article, prepared to commemorate the bicentenary of the shaking palsy, provides a historical state-of-the-art account of what has been achieved, the current situation, and how to progress toward resolving Parkinson's disease. © 2017 International Parkinson and Movement Disorder Society.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ involvement and pronounced racial and ethnic heterogeneity. The aims of the present work were (1) to describe the cumulative clinical characteristics of those patients included in the Spanish Rheumatology Society SLE Registry (RELESSER), focusing on the differences between patients who fulfilled the 1997 ACR-SLE criteria versus those with less than 4 criteria (hereafter designated as incomplete SLE (iSLE)) and (2) to compare SLE patient characteristics with those documented in other multicentric SLE registries. RELESSER is a multicenter hospital-based registry, with a collection of data from a large, representative sample of adult patients with SLE (1997 ACR criteria) seen at Spanish rheumatology departments. The registry includes demographic data, comprehensive descriptions of clinical manifestations, as well as information about disease activity and severity, cumulative damage, comorbidities, treatments and mortality, using variables with highly standardized definitions. A total of 4.024 SLE patients (91% with >= 4 ACR criteria) were included. Ninety percent were women with a mean age at diagnosis of 35.4 years and a median duration of disease of 11.0 years. As expected, most SLE manifestations were more frequent in SLE patients than in iSLE ones and every one of the ACR criteria was also associated with SLE condition; this was particularly true of malar rash, oral ulcers and renal disorder. The analysis-adjusted by gender, age at diagnosis, and disease duration-revealed that higher disease activity, damage and SLE severity index are associated with SLE [OR: 1.14; 95% CI: 1.08-1.20 (P < 0.001); 1.29; 95% CI: 1.15-1.44 (P < 0.001); and 2.10; 95% CI: 1.83-2.42 (P < 0.001), respectively]. These results support the hypothesis that iSLE behaves as a relative stable and mild disease. SLE patients from the RELESSER register do not appear to differ substantially from other Caucasian populations and although activity [median SELENA-SLEDA: 2 (IQ: 0-4)], damage [median SLICC/ACR/DI: 1 (IQ: 0-2)], and severity [median KATZ index: 2 (IQ: 1-3)] scores were low, 1 of every 4 deaths was due to SLE activity. RELESSER represents the largest European SLE registry established to date, providing comprehensive, reliable and updated information on SLE in the southern European population., We are grateful to GSK, Roche, Novartis and UCB for sponsorship of the registry, as well as to all employees of the Spanish Rheumatology Society Research Unit for their commitment and professionalism. Dr. Pego-Reigosa is supported by the Grant 316265 (BIOCAPS) from the European Union 7th Framework Programme (FP7/REGPOT-2012-2013.1).

Since 1995, at the Istituto Nazionale Neurologico "Carlo Besta" in Milan (INNCB,) 401 deep brain electrodes were implanted to treat several drug-resistant neurological syndromes (Fig. 1). More than 200 patients are still available for follow-up and therapeutical considerations. In this paper our experience is reviewed and pioneered fields are highlighted. The reported series of patients extends the use of deep brain stimulation beyond the field of Parkinson's disease to new fields such as cluster headache, disruptive behaviour, SUNCt, epilepsy and tardive dystonia. The low complication rate, the reversibility of the procedure and the available image guided surgery tools will further increase the therapeutic applications of DBS. New therapeutical applications are expected for this functional scalpel.

With the possibility of CT systems becoming more handy and sophisticated, intraoperative CT was introduced in a few neurosurgical Centres with better results in lesion removal and surgical outcome.At our Institution a mobile CT scanner was recently used for intraoperative evaluation (Philips Tomoscan M). For 27 tumour resections performed with a neuronavigation system, and 23 deep brain electrode positioning examinations, an intraoperative CT was employed. In addition the CT scanner was used in the recovery room for a postoperative control in 198 patients.Our preliminary experience used for a real time evaluation of the treated patients, permitted to verify an incomplete removal in 23/27 cases. Evaluation of stereotactic electrode position in relation to the planned target was also possible and demonstrated a correct position in 21 cases.Intraoperative CT scan is a useful system that permits to modify neuronavigation planning and is able to give information to the surgeon for better tumour removal, rule out possible hemorrhagic complications, and suitable deep brain electrode positioning.

The management of unruptured intracranial aneurysms requires knowledge of the natural history of these lesions and the risks of repairing them.A total of 2621 patients at 53 participating centers in the United States, Canada, and Europe were enrolled in the study, which had retrospective and prospective components. In the retrospective component, we assessed the natural history of unruptured intracranial aneurysms in 1449 patients with 1937 unruptured intracranial aneurysms; 727 of the patients had no history of subarachnoid hemorrhage from a different aneurysm (group 1), and 722 had a history of subarachnoid hemorrhage from a different aneurysm that had been repaired successfully (group 2). In the prospective component, we assessed treatment-related morbidity and mortality in 1172 patients with newly diagnosed unruptured intracranial aneurysms.In group 1, the cumulative rate of rupture of aneurysms that were less than 10 mm in diameter at diagnosis was less than 0.05 percent per year, and in group 2, the rate was approximately 11 times as high (0.5 percent per year). The rupture rate of aneurysms that were 10 mm or more in diameter was less than 1 percent per year in both groups, but in group 1, the rate was 6 percent the first year for giant aneurysms (or =25 mm in diameter). The size and location of the aneurysm were independent predictors of rupture. The overall rate of surgery-related morbidity and mortality was 17.5 percent in group 1 and 13.6 percent in group 2 at 30 days and was 15.7 percent and 13.1 percent, respectively, at 1 year. Age independently predicted surgical outcome.The likelihood of rupture of unruptured intracranial aneurysms that were less than 10 mm in diameter was exceedingly low among patients in group 1 and was substantially higher among those in group 2. The risk of morbidity and mortality related to surgery greatly exceeded the 7.5-year risk of rupture among patients in group 1 with unruptured intracranial aneurysms smaller than 10 mm in diameter.

Supplemental Digital Content is available in the text, The aim of the study was to profile those patients included in the RELESSER registry with histologically proven renal involvement in order to better understand the current state of lupus nephritis (LN) in Spain. RELESSER-TRANS is a multicenter cross-sectional registry with an analytical component. Information was collected from the medical records of patients with systemic lupus erythematosus who were followed at participating rheumatology units. A total of 359 variables including demographic data, clinical manifestations, disease activity, severity, comorbidities, LN outcome, treatments, and mortality were recorded. Only patients with a histological confirmation of LN were included. We performed a descriptive analysis, chi-square or Student's t tests according to the type of variable and its relationship with LN. Odds ratio and confidence intervals were calculated by using simple logistic regression. LN was histologically confirmed in 1092/3575 patients (30.5%). Most patients were female (85.7%), Caucasian (90.2%), and the mean age at LN diagnosis was 28.4 ± 12.7 years. The risk for LN development was higher in men (M/F:47.85/30.91%, P

Facial nerve injuries produce lagophthalmos and consequent ocular disease caused by corneal exposure. The management of the affected eye in patients with facial palsy has been improved. Previously ointment, eye drops, taping, partial or complete tarsorrhaphy was the primary treatment of the inability to close the eyelid. Other mechanical techniques for reanimating lid closure, including palpebral springs, encircling the upper and lower eyelids with silicone or fascia lata, and temporalis muscle transfer. The most popular and widely used static procedure in facial nerve palsy is the upper eyelid gold weight implant. This procedure is the goal of the treatment for the restoration of function and cosmesis to the paralyzed eyelids. The surgical technique used for lid load insertion are described below.

Neurofibromatosis type 1 (NF1) is a common tumor predisposition syndrome in which glioma is one of the prevalent tumors. Gliomagenesis in NF1 results in a heterogeneous spectrum of low- to high-grade neoplasms occurring during the entire lifespan of patients. The pattern of genetic and epigenetic alterations of glioma that develops in NF1 patients and the similarities with sporadic glioma remain unknown. Here, we present the molecular landscape of low- and high-grade gliomas in patients affected by NF1 (NF1-glioma). We found that the predisposing germline mutation of the NF1 gene was frequently converted to homozygosity and the somatic mutational load of NF1-glioma was influenced by age and grade. High-grade tumors harbored genetic alterations of TP53 and CDKN2A, frequent mutations of ATRX associated with Alternative Lengthening of Telomere, and were enriched in genetic alterations of transcription/chromatin regulation and PI3 kinase pathways. Low-grade tumors exhibited fewer mutations that were over-represented in genes of the MAP kinase pathway. Approximately 50% of low-grade NF1-gliomas displayed an immune signature, T lymphocyte infiltrates, and increased neo-antigen load. DNA methylation assigned NF1-glioma to LGm6, a poorly defined Isocitrate Dehydrogenase 1 wild-type subgroup enriched with ATRX mutations. Thus, the profiling of NF1-glioma defined a distinct landscape that recapitulates a subset of sporadic tumors. An integrated analysis of glioma samples from patients with neurofibromatosis 1 annotates their mutational, epigenetic, transcriptional, and immunological features and uncovers similitudes with a subset of sporadic gliomas.

Purpose: The aims of patients’ radiological surveillance are to: ascertain relapse; apply second-line therapy; accrue patients in phase 1/2 protocols if second-line therapy is not standardized/curative; and assess/treat iatrogenic effects. To lessen the emotional and socioeconomic burdens for patients and families, we ideally need to establish whether scheduled radiological surveillance gives patients a better outcome than waiting for symptoms and signs to appear. Methods: We analyzed a prospective series of 160 newly-diagnosed and treated pediatric/adolescent patients with intracranial ependymoma, comparing patients with recurrent disease identified on scheduled MRI (the RECPT group; 34 cases) with those showing signs/symptoms of recurrent disease (the SYMPPT group; 16 cases). The median follow-up was 67 months. Results: No significant differences emerged between the two groups in terms of gender, age, tumor grade/site, shunting, residual disease, or type of relapse (local, distant, or concomitant). The time to relapse (median 19 months; range 5–104) and the MRI follow-up intervals did not differ between the SYMPPT and RECPT groups. The presence of signs/symptoms was an unfavorable factor for overall survival (OS) after recurrence (5-year OS: 8% vs. 37%, p = 0.001). On multivariable analysis, an adjusted model confirmed a significantly worse OS in the SYMPPT than in the RECPT patients. Conclusions: Symptomatic relapses carried a significantly worse survival for ependymoma patients than recurrences detected by MRI alone. It would therefore be desirable to identify recurrences before symptoms develop. Radiological follow-up should be retained in ependymoma patient surveillance because there is a chance of salvage treatment for relapses found on MRI

Ring chromosome 14 [r(14)] is a rare disorder. The aim of this study was to describe two new cases of r(14) drug-resistant epilepsy, and, through an extensive review of literature, highlight those epileptological features which are more commonly found and which may help in early diagnosis, genetic counseling, and treatment. Epilepsy onset in r(14) syndrome takes place during the first year of life; seizures are generalized or focal and less frequently myoclonic. Seizures might be induced by fever. Focal seizures are characterized by staring, eye or head deviation, respiratory arrest, swallowing, and hypertonia/hypotonia or clonic movements. Ictal EEG might show both focal and diffuse discharges. Interictal EEG reveals mainly focal abnormalities. Mental retardation represents a constant feature. Neurological assessment yields a delay in motor skill acquisition and less frequently both pyramidal and cerebellar signs. Dysmorphic features are evident in the majority of cases. Epilepsy associated with r(14) has many features that entail a challenging diagnostic process. The reported cases of r(14)-related epilepsy seem to highlight a series of common elements which may be helpful in pointing the clinician towards a correct diagnosis.

Background This prospective study stratified patients by surgical resection (complete = NED vs incomplete = ED) and centrally reviewed histology (World Health Organization [WHO] grade II vs III). Methods WHO grade II/NED patients received focal radiotherapy (RT) up to 59.4 Gy with 1.8 Gy/day. Grade III/NED received 4 courses of VEC (vincristine, etoposide, cyclophosphamide) after RT. ED patients received 1-4 VEC courses, second-look surgery, and 59.4 Gy followed by an 8-Gy boost in 2 fractions on still measurable residue. NED children aged 1-3 years with grade II tumors could receive 6 VEC courses alone. Results From January 2002 to December 2014, one hundred sixty consecutive children entered the protocol (median age, 4.9 y; males, 100). Follow-up was a median of 67 months. An infratentorial origin was identified in 110 cases. After surgery, 110 patients were NED, and 84 had grade III disease. Multiple resections were performed in 46/160 children (28.8%). A boost was given to 24/40 ED patients achieving progression-free survival (PFS) and overall survival (OS) rates of 58.1% and 68.7%, respectively, in this poor prognosis subgroup. For the whole series, 5-year PFS and OS rates were 65.4% and 81.1%, with no toxic deaths. On multivariable analysis, NED status and grade II were favorable for OS, and for PFS grade II remained favorable. Conclusions In a multicenter collaboration, this trial accrued the highest number of patients published so far, and results are comparable to the best single-institution series. The RT boost, when feasible, seemed effective in improving prognosis. Even after multiple procedures, complete resection confirmed its prognostic strength, along with tumor grade. Biological parameters emerging in this series will be the object of future correlatives and reports.

To prospectively determine the sensitivity and specificity of functional magnetic resonance (MR) imaging for mapping language and motor functions in patients with a focal mass adjacent to eloquent cortex, by using intraoperative electrocortical mapping (ECM) as the reference standard.The ethics committee approved the study, and patients gave written informed consent. Thirty-four consecutive patients (16 women, 18 men; mean age, 43.2 years) were included who met the following three criteria: They had a focal mass in or adjacent to eloquent cortex of the language or motor system, they had the ability to perform the functional MR imaging task, and they had to undergo surgery with intraoperative ECM. Functional MR imaging with verb generation (n = 17) or finger tapping of the contralateral hand (n = 17) was performed at 1.5 T with a block design and an echo-planar gradient-echo T2*-weighted sequence. Cortex essential for language or hand motor functions was mapped with ECM. A site-by-site comparison between functional MR imaging and ECM was performed with the aid of a neuronavigational device. Sensitivity and specificity were calculated according to task performed, histopathologic findings, and tumor grade. Exact 95% confidence intervals were calculated for each sensitivity and specificity value.For 34 consecutive patients, there were 28 with gliomas, two with metastases, one with meningioma, and three with cavernous angiomas. A total of 251 cortical sites were tested with ECM; overall functional MR imaging sensitivity and specificity were 83% and 82%, respectively. Sensitivity (65%) was lower and specificity (93%) was higher in World Health Organization grade IV gliomas compared with grade II (sensitivity, 93%; specificity, 79%) and III (sensitivity, 93%; specificity, 76%) gliomas. At 3 months after surgery, language proficiency was unchanged in 15 patients; functionality of the contralateral arm was unchanged in 14 patients and improved in one patient.Functional MR imaging is a sensitive and specific method for mapping language and motor functions.

We read with interest the report by Romito et al. about a patient with fixed dystonia who responded to motor cortex stimulation.1 In our view, their conclusions are limited by uncertainties about the diagnosis and shortcomings in the evaluation of the therapeutic response. These aspects are important when an invasive neurosurgical procedure is proposed for consideration in similar cases. The diagnosis of psychogenic dystonia is excluded by the authors with the statement that “nothing indicated somatoform or psychogenic disorder.”1 This diagnosis should be suspected when patients have fixed and painful posturing of the neck or limbs, which renders them unable to carry out basic daily activities.2 Possible, probable, documented, and clinically established categories of certainty can be established by applying Fahn and Williams' criteria.3 Only 10% of the fixed dystonia cohort evaluated prospectively with a standardized neuropsychiatric protocol by Schrag et al. did not meet criteria for psychogenic dystonia.4 Furthermore, the posture exhibited by this patient is similar to …