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Abstract Nicotinamide adenine dinucleotide (NAD) replenishment therapy using nicotinamide riboside (NR) shows promise for Parkinson’s disease (PD) and other neurodegenerative disorders. However, the optimal dose of NR remains unknown, and doses exceeding 2000 mg daily have not been tested in humans. To evaluate the safety of high-dose NR therapy, we conducted a single-center, randomized, placebo-controlled, double-blind, phase I trial on 20 individuals with PD, randomized 1:1 on NR 1500 mg twice daily (n = 10) or placebo (n = 10) for four weeks. The trial was conducted at the Department of Neurology, Haukeland University Hospital, Bergen, Norway. The primary outcome was safety, defined as the frequency of moderate and severe adverse events. Secondary outcomes were tolerability defined as frequency of mild adverse events, change in the whole blood and urine NAD metabolome, and change in the clinical severity of PD, measured by MDS-UPDRS. All 20 participants completed the trial. The trial met all prespecified outcomes. NR therapy was well tolerated with no moderate or severe adverse events, and no significant difference in mild adverse events. NR therapy was associated with clinical improvement of total MDS-UPDRS scores. However, this change was also associated with a shorter interval since the last levodopa dose. NR greatly augmented the blood NAD metabolome with up to 5-fold increase in blood NAD+ levels. While NR-recipients exhibited a slight initial rise in serum homocysteine levels, the integrity of the methyl donor pool remained intact. Our results support extending the dose range of NR in phase II clinical trials to 3000 mg per day, with appropriate safety monitoring. Clinicaltrials.gov identifier: NCT05344404.

Damage to the orbitofrontal cortex (OFC) often occurs following a traumatic brain injury (TBI) and can lead to complex behavioral changes, including difficulty with attention and concentration. We investigated the effects of musical training on patients with behavioral and cognitive deficits following a mild traumatic brain injury (mTBI) and found significant functional neuro-plastic changes in the OFC’s networks. The results from neuropsychological tests revealed an improved cognitive performance. Moreover, six out of seven participants in this group returned to work post intervention and reported improved well-being and social behavior. In this study, we explore the functional changes in OFC following music-supported intervention in reference to connecting networks that may be responsible for enhanced social interaction. Furthermore, we discuss the factor of dopamine release during playing as an element providing a possible impact on the results. The intervention consisted of playing piano, two sessions per week in 8 weeks, 30 min each time, with an instructor. Additional playing was required with a minimum of 15 min per day at home. Mean time playing piano in reference to participant’s report was 3 h per week during the intervention period. Three groups participated, one mTBI group (n = 7), two control groups consisting of healthy participants, one with music training (n = 11), and one baseline group without music training (n = 12). Participants in the clinical group had received standardized cognitive rehabilitation treatment during hospitalization without recovering from their impairments. The intervention took place 2 years post injury. All participants were assessed with neuropsychological tests and with both task and resting-state functional magnetic resonance imaging (fMRI) pre-post intervention. The results demonstrated a significant improvement of neuropsychological tests in the clinical group, consistent with fMRI results in which there were functional changes in the orbitofrontal networks (OFC). These changes were concordantly seen both in a simple task fMRI but also in resting-state fMRI, which was analyzed with dynamic causal modeling (DCM). We hypothesized that playing piano, as designed in the training protocol, may provide a positive increase in both well-being and social interaction. We suggest that the novelty of the intervention may have clinical relevance for patients with behavioral problems following a TBI.

Previous research has demonstrated that people with Parkinson's disease (PD) have difficulties with the perceptual discrimination of rhythms, relative to healthy controls. It is not however clear if this applies only to simpler rhythms (a so called "beat-based" deficit), or if it is a more generalized deficit that also applies to more complex rhythms. Further insight into how people with PD process and perceive rhythm can refine our understanding of the well known problems of temporal processing in the disease. In this study, we wanted to move beyond simple/complex-dichotomy in previous studies, and further investigate the effect of tempo on the perception of musical rhythms. To this end, we constructed ten musical rhythms with a varied degree of complexity across three different tempi. Nineteen people with PD and 19 healthy controls part-took in an internet based listening survey and rated 10 different musical rhythms for complexity and likeability. In what we believe is the first study to do so, we asked for the participants subjective ratings of individual rhythms and not their capacity to directly compare or discriminate between them. We found an overall between-group difference in complexity judgments that was modulated by tempo, but not level of complexity. People with PD rated all rhythms as more complex across tempi, with significant group differences in complexity ratings at 120 and 150bpm, but not at 90bpm. Our analysis found a uniform elevated baseline for complexity judgments in the PD-group, and a strong association between the two groups' rank-ordering the rhythms for complexity. This indicates a preserved ability to discriminate between relative levels of complexity. Finally, the two groups did not significantly differ in their subjective scoring of likeability, demonstrating a dissimilarity between judgment of complexity and judgment of likeability between the two groups. This indicates different cognitive operations for the two types of judgment, and we speculate that Parkinson's disease affects judgment of complexity but not judgment of likeability.

Patients with autoimmune myasthenia gravis (MG) should be further classified before initiating therapy, as treatment response varies for ocular versus generalised, early onset versus late onset, and acetylcholine receptor antibody positive versus MuSK antibody positive disease. Most patients need immunosuppression in addition to symptomatic therapy. Prednisolone and azathioprine represent first choice drugs, whereas several second choice options are recommended and should be considered. Thymectomy should be undertaken in MG with thymoma and in generalised, early-onset MG. For MG crises and other acute exacerbations, intravenous immunoglobulin (IvIg) and plasma exchange are equally effective and safe treatments. Children and females in child bearing age need special attention regarding potential side effects of immunosuppressive therapy. MG pathogenesis is known in detail, but the immune therapy is still surprisingly unspecific, without a pin-pointed attack on the defined disease-inducing antigen-antibody reaction being available.

Background There is no consensus on the management of incidental meningiomas. The literature on long-term growth dynamics is sparse and the natural history of these tumors remains to be illuminated. Methods We prospectively assessed long-term tumor growth dynamics and survival rates during active monitoring of 62 patients (45 female, mean age 63.9 years) harboring 68 tumors. Clinical and radiological data were obtained every 6 months for 2 years, annually until 5 years, then every second year. Results The natural progression of incidental meningiomas during 12 years of monitoring was growth (P  < .001). However, mean growth decelerated at 1.5 years and became insignificant after 8 years. Self-limiting growth patterns were seen in 43 (63.2%) tumors, non-decelerating in 20 (29.4%) and 5 (7.4%) were inconclusive due to  ≤ 2 measurements. Decelerating growth persisted once established. Within 5 years, 38 (97.4%) of 39 interventions were initiated. None developed symptoms prior to intervention. Large tumors (P  < .001) involving venous sinuses (P  = .039) grew most aggressively. Since inclusion 19 (30.6%) patients have died of unrelated causes and 2 (3%) from grade 2 meningiomas. Conclusion Active monitoring seems a safe and appropriate first-line management of incidental meningiomas. Intervention was avoided in  > 40% with indolent tumors in this cohort. Treatment was not compromised by tumor growth. Clinical follow-up seems sufficient beyond 5 years if self-limiting growth is established. Steady or accelerating growth warrant monitoring until they reach a stable state or intervention is initiated. [ABSTRACT FROM AUTHOR]

Background: Common genetic variance in apolipoprotein E (APOE), β‐glucocerebrosidase (GBA), microtubule‐associated protein tau (MAPT), and α‐synuclein (SNCA) has been linked to cognitive decline in Parkinson's disease (PD), although studies have yielded mixed results. Objectives: To evaluate the effect of genetic variants in APOE, GBA, MAPT, and SNCA on cognitive decline and risk of dementia in a pooled analysis of six longitudinal, non‐selective, population‐based cohorts of newly diagnosed PD patients. Methods: 1002 PD patients, followed for up to 10 years (median 7.2 years), were genotyped for at least one of APOE‐ε4, GBA mutations, MAPT H1/H2, or SNCA rs356219. We evaluated the effect of genotype on the rate of cognitive decline (Mini‐Mental State Examanation, MMSE) using linear mixed models and the development of dementia (diagnosed using standardized criteria) using Cox regression; multiple comparisons were accounted for using Benjamini−Hochberg corrections. Results: Carriers of APOE‐ε4 (n = 281, 29.7%) and GBA mutations (n = 100, 10.3%) had faster cognitive decline and were at higher risk of progression to dementia (APOE‐ε4, HR 3.57, P < 0.001; GBA mutations, HR 1.76, P = 0.001) than non‐carriers. The risk of cognitive decline and dementia (HR 5.19, P < 0.001) was further increased in carriers of both risk genotypes (n = 23). No significant effects were observed for MAPT or SNCA rs356219. Conclusions: GBA and APOE genotyping could improve the prediction of cognitive decline in PD, which is important to inform the clinical trial selection and potentially to enable personalized treatment © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Background The number of incidental meningiomas has increased because of the increased availability of neuroimaging. Lack of prospective data on the natural history makes the optimal management unclear. We conducted a 5-year prospective study of incidental meningiomas to identify risk factors for tumor growth. Methods Sixty-four of 70 consecutive patients with incidental meningioma were included. Clinical and radiological status was obtained at 0, 0.5, 1, 1.5, 2, 3, 4, and 5 years. GammaPlan and mixed linear regression modeling were utilized for volumetric analysis with primary endpoint tumor growth. Results None of the patients developed tumor-related symptoms during the study period, although 48 (75%) tumors increased (>15%), 13 (20.3%) remained unchanged, and 3 (4.7%) decreased (>15%) in volume. Mean time to growth was 2.2 years (range, 0.5-5.0 years). The growth pattern was quasi-exponential in 26%, linear in 17%, sigmoidal in 35%, parabolic in 17%, and continuous reduction in 5%. There was significant correlation among growth rate, larger baseline tumor volume (P <.001), and age in years (<55 y: 0.10 cm3/y, 55-75 y: 0.24 cm3/y, and >75 y: 0.85 cm3/y). Conclusion The majority of meningiomas will eventually grow. However, more than 60% display a self-limiting growth pattern. Our study provides level-2 evidence that asymptomatic tumors can be safely managed utilizing serial imaging until persistent radiological and/or symptomatic growth. [ABSTRACT FROM AUTHOR]

The Joint Editors-in-Chief have retracted this article [1] at the request of the University of Bergen and the Norwegian Board of Health Supervision. [ABSTRACT FROM AUTHOR]

Previous research has demonstrated that people with Parkinson’s disease (PD) have difficulties with the perceptual discrimination of rhythms, relative to healthy controls. It is not however clear if this applies only to simpler rhythms (a so called “beat-based” deficit), or if it is a more generalized deficit that also applies to more complex rhythms. Further insight into how people with PD process and perceive rhythm can refine our understanding of the well known problems of temporal processing in the disease. In this study, we wanted to move beyond simple/complex-dichotomy in previous studies, and further investigate the effect of tempo on the perception of musical rhythms. To this end, we constructed ten musical rhythms with a varied degree of complexity across three different tempi. Nineteen people with PD and 19 healthy controls part-took in an internet based listening survey and rated 10 different musical rhythms for complexity and likeability. In what we believe is the first study to do so, we asked for the participants subjective ratings of individual rhythms and not their capacity to directly compare or discriminate between them. We found an overall between-group difference in complexity judgments that was modulated by tempo, but not level of complexity. People with PD rated all rhythms as more complex across tempi, with significant group differences in complexity ratings at 120 and 150bpm, but not at 90bpm. Our analysis found a uniform elevated baseline for complexity judgments in the PD-group, and a strong association between the two groups’ rank-ordering the rhythms for complexity. This indicates a preserved ability to discriminate between relative levels of complexity. Finally, the two groups did not significantly differ in their subjective scoring of likeability, demonstrating a dissimilarity between judgment of complexity and judgment of likeability between the two groups. This indicates different cognitive operations for the two types of judgment, and we speculate that Parkinson’s disease affects judgment of complexity but not judgment of likeability. [ABSTRACT FROM AUTHOR]

Damage to the orbitofrontal cortex (OFC) often occurs following a traumatic brain injury (TBI) and can lead to complex behavioral changes, including difficulty with attention and concentration. We investigated the effects of musical training on patients with behavioral and cognitive deficits following a mild traumatic brain injury (mTBI) and found significant functional neuro-plastic changes in the OFC's networks. The results from neuropsychological tests revealed an improved cognitive performance. Moreover, six out of seven participants in this group returned to work post intervention and reported improved well-being and social behavior. In this study, we explore the functional changes in OFC following music-supported intervention in reference to connecting networks that may be responsible for enhanced social interaction. Furthermore, we discuss the factor of dopamine release during playing as an element providing a possible impact on the results. The intervention consisted of playing piano, two sessions per week in 8 weeks, 30 min each time, with an instructor. Additional playing was required with a minimum of 15 min per day at home. Mean time playing piano in reference to participant's report was 3 h per week during the intervention period. Three groups participated, one mTBI group (n = 7), two control groups consisting of healthy participants, one with music training (n = 11), and one baseline group without music training (n = 12). Participants in the clinical group had received standardized cognitive rehabilitation treatment during hospitalization without recovering from their impairments. The intervention took place 2 years post injury. All participants were assessed with neuropsychological tests and with both task and resting-state functional magnetic resonance imaging (fMRI) pre-post intervention. The results demonstrated a significant improvement of neuropsychological tests in the clinical group, consistent with fMRI results in which there were functional changes in the orbitofrontal networks (OFC). These changes were concordantly seen both in a simple task fMRI but also in resting-state fMRI, which was analyzed with dynamic causal modeling (DCM). We hypothesized that playing piano, as designed in the training protocol, may provide a positive increase in both well-being and social interaction. We suggest that the novelty of the intervention may have clinical relevance for patients with behavioral problems following a TBI. [ABSTRACT FROM AUTHOR]

Behavioral studies indicate that persons with Parkinson's disease have complexity dependent problems with the discrimination of auditory rhythms. Furthermore, neuroimaging studies show that rhythm processing activates many brain areas that overlap with areas affected by Parkinson's disease (PD). This study sought to investigate the neural correlates of rhythm processing in PD and healthy controls, with a particular focus on rhythmic complexity. We further aimed to investigate differences in brain activation during initial phases of rhythm processing. Functional magnetic resonance imaging was used to scan 15 persons with Parkinson's disease and 15 healthy controls while they listened to musical rhythms with two different levels of complexity. Rhythmic complexity had no significant effect on brain activations, but patients and controls showed differences in areas related to temporal auditory processing, notably bilateral planum temporale and inferior parietal lobule. We found indications of a particular sequential or phasic activation pattern of brain activity, where activity in caudate nucleus in the basal ganglia was time‐displaced by activation in the saliency network—comprised of anterior cingulate cortex and bilateral anterior insula—and cortical and subcortical motor areas, during the initial phases of listening to rhythms. We relate our findings to core PD pathology, and discuss the overall, rhythm processing related hyperactivity in PD as a possible dysfunction in specific basal ganglia mechanisms, and the phasic activation pattern in PD as a reflection of a lack of preparatory activation of task‐relevant brain networks for rhythm processing in PD. [ABSTRACT FROM AUTHOR]

Objectives: Olfactory dysfunction has been related to cognitive deficits in Parkinson's disease (PD), but evidence is conflicting and little is known about the relationship between these symptoms in early PD. Our objective was to study the association between smell deficits measured with a simple odor identification test at diagnosis of PD and the subsequent risk of cognitive decline. Materials & methods: One hundred and ninety two PD patients from a population‐based study were examined at time of diagnosis, before initiation of dopaminergic treatment, with follow‐up of 177 patients after 3 years, 162 patients after 5 years and 146 patients after 7 years. Cognitive function was assessed repeatedly with tests of global cognition, verbal memory, visuospatial abilities, processing speed, and executive function. Olfactory function was tested with a simple odor identification test at baseline. Associations between outcome measures and hyposmia were assessed by linear mixed effects models. Results: After 7 years, there were significant differences in global cognition (B: 1.96 (95% CI: 0.68, 3.24), P = 0.0031), verbal memory including immediate recall (B: 5.36 (95% CI: 2.04, 8.67), P = 0.0018) and delayed recall (B: 1.55 (95% CI: 0.51, 2.59), P = 0.0041) and word reading speed (B: 6.90 (95% CI: 2.17, 11.63), P = 0.0048) between hyposmic and normosmic PD patients. Conclusions: The decline of cognitive function in early PD is more rapid in patients with hyposmia at diagnosis, compared to normosmic ones. A simple smell test may contribute to identify patients at risk of accelerated decline in global cognition, verbal memory, and processing speed within the first 7 years from diagnosis. [ABSTRACT FROM AUTHOR]

Background and purpose: Myasthenia gravis (MG) is an autoimmune disease with muscular weakness as the only symptom, and often with immunosuppressive treatment. All these aspects could have relevance for the risk of infections as well as their prophylactic and curative treatment.Methods: This is a review article, where Web of Science has been searched for relevant key words and key word combinations. Full papers were selected first by title and then by abstract.Results and conclusions: MG can be triggered and worsened by infections. No virus or other pathogen has been proven to have a specific link to MG. Treatment with immunosuppressive drugs and thymectomy implies a slightly increased risk for infections. Infections should be actively treated, but a few antibiotics are avoided due to potential interference with neuromuscular transmission. Hospitalization and intensive care may be necessary during infections because of MG deterioration and risk of insufficient respiration. Vaccinations are generally recommended in MG, but live microorganisms should be avoided if possible in immunosuppressed patients. [ABSTRACT FROM AUTHOR]

Objective: We explored the effects of playing the piano on patients with cognitive impairment after mild traumatic brain injury (mTBI) and, addressed the question if this approach would stimulate neural networks in re-routing neural connections and link up cortical circuits that had been functional inhibited due to disruption of brain tissue. Functional neuroimaging scans (fMRI) and neuropsychological tests were performed pre-post intervention. Method: Three groups participated, one mTBI group (n = 7), two groups of healthy participants, one with music training (n = 11), one baseline group without music (n = 12). The music groups participated in 8 weeks music-supported intervention. Results: The patient group revealed training-related neuroplasticity in the orbitofrontal cortex. fMRI results fit well with outcome from neuropsychological tests with significant enhancement of cognitive performance in the music groups. Ninety per cent of mTBI group returned to work post intervention. Conclusion: Here, for the first time, we demonstrated behavioural improvements and functional brain changes after 8 weeks of playing piano on patients with mTBI having attention, memory and social interaction problems. We present evidence for a causal relationship between musical training and reorganisation of neural networks promoting enhanced cognitive performance. These results add a novel music-supported intervention within rehabilitation of patients with cognitive deficits following mTBI. [ABSTRACT FROM AUTHOR]

Myasthenia gravis (MG) is an autoimmune disorder mediated by antibodies against proteins at the neuromuscular junction. Juvenile-onset MG (JMG) has been reported to have special characteristics. It is still unclear whether there are any pathogenic and genetic differences between juvenile and adult MG. In this study, we evaluated the clinical characteristics, autoantibody status (antibodies against AChR, MuSK, LRP4, titin and RyR) and genetic susceptibility (CHRNA1, CTLA4 and AIRE) in 114 Chinese JMG patients, and compared with 207 young adult MG patients (onset age 18-40 years). JMG patients were classified into two subgroups: the very early onset group (<8 years) and puberty onset group (8-18 years). The very early onset MG patients had a higher proportion of ocular MG and thymus hyperplasia, compared with puberty onset MG and young adult MG ( P < 0.05). AChR antibodies were found in majority of JMG patients and were associated with more severe disease ( P < 0.05), while other antibodies were rare in JMG. Moreover, the very early onset MG had a more prominent genetic predisposition than puberty and adult MG, affecting the susceptible genes CHRNA1 and CTLA4. JMG has the same pathogenic background as adult MG, but has typical clinical features and a prominent genetic predisposition in very early onset patients (<8 years). Specific therapeutic considerations are needed. [ABSTRACT FROM AUTHOR]

Background: Familial aggregation has been described in PD of both early and late onset, but has not been studied in a true population-based sample. Moreover, little is known about its association with disease progression and endophenotypes.Objectives: The objectives of this work were to determine familial aggregation of idiopathic PD in a population-based cohort and study the association with clinical endophenotypes and disease progression.Methods: We examined family history data from the Norwegian ParkWest study, a well-characterized, population-based cohort of incident PD patients and age-matched healthy controls. Family data were collected at baseline with a simplified questionnaire (192 cases and 193 controls) and after 3 years of longitudinal follow-up using an extended questionnaire (172 cases and 171 controls).Results: Compared to the controls, the PD patients had an increased relative risk of having a first-degree relative with PD when using the extended questionnaire (relative risk = 1.988; P = 0.036), but not when using the simplified questionnaire (relative risk = 1.453; P = 0.224). There was no significant difference in age of onset or motor subtype (P = 0.801). However, cases with a family history of PD had reduced progression over 7 years as measured by UPDRS II (P = 0.008) and smaller rate of decrease of MMSE (P = 0.046).Conclusions: Our findings confirm familial aggregation in a population-based cohort of idiopathic PD. Moreover, we show that positive family history of PD in patients is associated with a slower progression of PD symptoms and cognitive decline. © 2016 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Defining both a threshold of progression and the optimal endpoint for clinical trials on radiation therapy for benign meningiomas is difficult. In fact, the growth rates of meningiomas are variable, overall survival (OS) is often very long, and progression-free survival (PFS) requires long-term follow-up. To assess radiation response various strategies have been evaluated. Although most of the published studies describe the criteria for control assessment, there is no uniform definition. Volumetric analysis of magnetic resonance imaging (MRI) imaging has been proposed as the most appropriate method for detecting change in slowly evolving brain tumors. In this scenario, we analyzed this method in post-radiosurgical intracranial meningiomas as part of a prospective clinical trial. The primary aim of the present study was to validate a volumetric assessment method after fractionated radiosurgery or fractionated stereotactic radiotherapy (fSRS) for benign intracranial meningiomas. Secondary aims were evaluation of a cut-off to define progression, stable or partial response and volumetric response after fSRS treatment. To validate the volumetric assessment, we appraised delta values (ΔV) of volume variations. To evaluate tumor response, a volumetric analysis has been performed by means of co-registration of each follow-up MRI on baseline MRI and contouring of the lesion on each post-treatment exam. Overall, 150 patients were considered eligible for the purpose of the volumetric analysis. After a mean followup of 60.5 months (SD 17.45, median 59, range 14–101 months) the median reduction in tumor volume was -21.26%, (range -82.26% to 91.36%) to reach a median final tumor of 8.65 cm3 (range 0.38 - 56.28 cm3) that differed significantly from baseline (p < 0.001). Among 150 irradiated meningiomas, 75 (50%) ultimately regressed, 67 (45%) remained stable, and 8 (5%) progressed. Baseline volumes were similar in each group (p = 0.092), and final volumes were significantly larger in tumors that progressed (p < 0.001) supporting the use of a ΔV of 20% as a cutoff for progression. The mean %ΔV became significantly different by 10 months, with continued diversion up to 36 months. Our results suggest quantitative volumetric assessment of tumor response to fSRS may help clinicians to better understand early response profiles and provide a valuable tool for patient management following fSRS for meningiomas. [ABSTRACT FROM AUTHOR]

Background: Patients with meningiomas are typically treated with maximal safe surgical resection. After subtotal resection or at the time of tumor recurrence, stereotactic radiosurgery (SRS) is often used as the treatment of choice. While contrast-enhanced magnetic resonance imaging (MRI) is typically used for SRS target delineation, differentiating tumor growth from postoperative change can be challenging. 68Ga-DOTATATE, a positron emission tomography (PET) radiotracer targeting the somatostatin receptor type 2 (SSTR2), has been shown to be a reliable biomarker of meningiomas. Objective: The aim of this study was to evaluate the impact of 68Ga-DOTATATE on treatment planning in patients who had previously undergone meningioma resection. Methods: We present a consecutive case series of 13 patients with histologically-proven meningioma who received a 68Ga-DOTATATE PET between April 2019 and April 2021. Treatment planning was done at first using MRI only. The DOTATATE-PET images were then used to assess the accurate identification of tumor. Results: Ten of the patients had WHO grade 2 meningioma and three patients had grade 1 tumor. Nine patients had recurrent meningiomas and four patients had newly diagnosed disease. Overall, the 68Ga-DOTATATE PET scan led to a change in the previously formulated treatment plans in 6 of 13 patients. Additionally, 8 of the 13 patients had foci of disease not appreciated on post-contrast MRI. Conclusion: In this series, incorporation of 68GaDOTATATE PET imaging had clinical utility for most patients in whom it was used. It proved particularly useful in demonstrating intraosseous meningiomas, differentiating between recurrence and post-operative changes, and identifying sub-centimeter foci of disease. We recommend incorporating this imaging method as part of postoperative SRS for patients with meningiomas. [ABSTRACT FROM AUTHOR]

Objectives There are limited data on treatment effect in early and drug-naïve Parkinson's disease ( PD) outside of clinical trials. We sought to review the treatment effects on motor symptoms in early, unselected PD patients. Methods We included 183 drug-naïve patients from a longitudinal cohort ( The Norwegian Park West study). At the time of diagnosis, motor symptoms were assessed and rated. Treatment was unrestricted, aimed at treating each patient optimally. Patients were reassessed after 12 months, and then grouped according to treatment: No dopaminergic treatment ( NDT), dopamine agonists ( DA) or levodopa. All strategies could be combined with monoamine oxidase B inhibitors. Results In general, the chosen treatment was coherent with current practice. During follow-up, patients given NDT ( n = 40) had unaltered clinical motor symptoms, as opposed to improvement in the DA- and levodopa-treated patients ( n = 140). The overall improvement in these two groups was fairly similar, but axial symptoms did not improve in levodopa-treated patients as opposed to the younger DA-treated patients. Conclusions Twelve months after the diagnosis, motor symptoms in approximately one-fifth of PD patients remained clinically stable. Tremor, bradykinesia and rigidity improved in the dopaminergic-treated patients. Axial symptoms were more treatment resistant, and the different symptomatic effects found between treatment strategies may be age related. [ABSTRACT FROM AUTHOR]

Objectives Autonomic symptoms are present in early stages of Parkinson's disease (PD), but evidence on how they are influenced by dopaminergic treatment remains unclear. The aim of this study was to investigate the impact of dopaminergic treatment on autonomic symptoms in early PD in a population-based cohort. Methods A total of 171 drug-naive patients with PD were investigated at diagnosis and 12 months later. Orthostatic blood pressure was measured, and autonomic symptoms were assessed by a preliminary version of the Movement Disorders Society-sponsored new version of the Unified Parkinson's Disease Rating Scale (range 0-4). Results In the 82% using dopaminergic treatment after 1 year, constipation and orthostatic blood pressure drop increased. There was a tendency towards increased orthostatic dizziness and urinary dysfunction. Dysphagia scores were reduced, and this was associated with higher levodopa-equivalent daily dose. Conclusions Dopaminergic treatment during the first year after initiation seems to have only a minor impact on autonomic symptoms in early PD. It may increase constipation and orthostatic dizziness, while dysphagia can improve. Autonomic symptoms remained mild after 1 year of dopaminergic treatment. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder where patients exhibit impairments in speech production. Few studies have investigated the influence of music interventions on vocal abilities of individuals with PD.Objectives: To evaluate the influence of a group voice and singing intervention on speech, singing, and depressive symptoms in individuals with PD.Methods: Ten patients diagnosed with PD participated in this one-group, repeated measures design study. Participants received the sixty-minute intervention, in a small group setting once a week for 20 consecutive weeks. Speech and singing quality were acoustically analyzed using a KayPentax Multi-Dimensional Voice Program, voice ability using the Voice Handicap Index (VHI), and depressive symptoms using the Montgomery and Asberg Depression rating scale (MADRS). Measures were taken at baseline (Time 1), after 10 weeks of weekly sessions (Time 2), and after 20 weeks of weekly sessions (Time 3).Results: Significant changes were observed for five of the six singing quality outcomes at Time 2 and 3, as well as voice range and the VHI physical subscale at Time 3. No significant changes were found for speaking quality or depressive symptom outcomes; however, there was an absence of decline on speaking quality outcomes over the intervention period.Conclusions: Significant improvements in singing quality and voice range, coupled with the absence of decline in speaking quality support group singing as a promising intervention for persons with PD. A two-group randomized control study is needed to determine whether the intervention contributes to maintenance of speaking quality in persons with PD. [ABSTRACT FROM AUTHOR]

The article discusses a study that determined if congenital myasthenic syndromes (CMSs) due to RAPSN or DOK7 mutations may be mistaken for seronegative Myasthenia gravis (SNMG). The study involved the examination for the N88K and c.1124_1127dupTGCC mutation of 74 Norwegian patients with SNMG and 37 healthy controls. Results revealed that 1 patient was homozygous for N88K and 2 carriers are of N88K mutation leading to the conclusion that rapsn CMS may be falsely identified as SNMG.

Vefring H, Haugarvoll K, Tysnes O-B, Larsen JP, Kurz MW, for the Norwegian ParkWest Study group. The role of APOE alleles in incident Parkinson's disease. The Norwegian ParkWest Study. Acta Neurol Scand: 2010: 122: 438-441. © 2010 John Wiley & Sons A/S. Apolipoprotein E ( APOE) gene alleles have been associated with various neurodegenerative disorders. However, there have been conflicting reports on associations between APOE alleles and Parkinson's disease (PD) and age at onset in PD. There exist no data on APOE alleles in an unselected cohort of patients with incident PD. To determine the role of APOE alleles in PD and age of onset in PD at time of diagnosis, 203 patients with incident PD and 187 healthy control subjects from Western and Southern Norway were investigated according to their APOE allele status. No association was observed between any APOE alleles and susceptibility to PD or age at onset in PD. In our cohort of unselected, incident PD patients APOE alleles do not seem to play a role for development of PD. Prospective, long-term follow-up may still reveal associations between APOE alleles and clinical and neuropsychological progression in PD. [ABSTRACT FROM AUTHOR]

Both environmental and genetic factors contribute to the development of Parkinson's disease (PD). We have examined environmental risk factors in a Norwegian population of incident PD patients and controls, the Norwegian ParkWest study. All five neurological wards in the study area of Western Norway participated in the study. A 4-step diagnostic procedure was used to establish a representative cohort of patients with incident PD at a high level of diagnostic accuracy. 212 incident PD patients and 175 age- and gender-matched controls were included. PD patients and controls were asked for information on occupation, education, exposure to pesticides, tobacco, alcohol, and caffeine. Agricultural work was associated with a higher risk of PD (OR 1.75 (1.03-3.0) P = 0.009). There were no differences as to other occupations. Smoking (OR 0.63 (0.42-0.95) P = 0.016) and alcohol use (OR 0.55 P = 0.008) were associated with a lower risk for PD. Interestingly, this inverse association was only seen in postural instability gait difficulties (PIGD) PD ( P = 0.046 for smoking, P = 0.07 for alcohol consumption), and not in tremor dominant (TD) PD which was similar to controls. Consumption of coffee was lower in PD patients (3.3 ± 1.8 cups per day vs. 3.8 ± 2.0 in controls P = 0.02). In the regression model including intake of alcohol, coffee, and smoke, only coffee ( P = 0.007) and alcohol intake ( P = 0.021) remained significant whereas smoking was no longer significant. Thus, it seems as though only coffee intake reduces the risk of PD in general while associations to alcohol and smoking differ between PIGD and TD-PD patients. © 2010 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Background: Important progress has been made in our understanding of the autoimmune neuromuscular transmission (NMT) disorders; myasthenia gravis (MG), Lambert–Eaton myasthenic syndrome (LEMS) and neuromyotonia (Isaacs’ syndrome). Methods: To prepare consensus guidelines for the treatment of the autoimmune NMT disorders, references retrieved from MEDLINE, EMBASE and the Cochrane Library were considered and statements prepared and agreed on by disease experts. Conclusions: Anticholinesterase drugs should be given first in the management of MG, but with some caution in patients with MuSK antibodies (good practice point). Plasma exchange is recommended in severe cases to induce remission and in preparation for surgery (recommendation level B). IvIg and plasma exchange are effective for the treatment of MG exacerbations (recommendation level A). For patients with non-thymomatous MG, thymectomy is recommended as an option to increase the probability of remission or improvement (recommendation level B). Once thymoma is diagnosed, thymectomy is indicated irrespective of MG severity (recommendation level A). Oral corticosteroids are first choice drugs when immunosuppressive drugs are necessary (good practice point). When long-term immunosuppression is necessary, azathioprine is recommended to allow tapering the steroids to the lowest possible dose whilst maintaining azathioprine (recommendation level A). 3,4-Diaminopyridine is recommended as symptomatic treatment and IvIG has a positive short-term effect in LEMS (good practice point). Neuromyotonia patients should be treated with an antiepileptic drug that reduces peripheral nerve hyperexcitability (good practice point). For paraneoplastic LEMS and neuromyotonia optimal treatment of the underlying tumour is essential (good practice point). Immunosuppressive treatment of LEMS and neuromyotonia should be similar to MG (good practice point). [ABSTRACT FROM AUTHOR]

Apathy is a common behavioural problem in Parkinson’s disease (PD), with important clinical consequences for patients and their families. However, little is known about apathy in early PD. We examined the frequency and clinical characteristics of apathy in 175 nondemented, drug-naïve patients with newly diagnosed PD and 165 control subjects matched for age, sex and education level in Western and Southern Norway. All participants underwent a comprehensive neurological, psychiatric and neuropsychological evaluation. Apathy was diagnosed based on Neuropsychiatric Inventory assessment and recently proposed consensus criteria. Apathy was found in 22.9% of the PD patients, of whom 37.5% had significant depressive symptoms, whereas none of the control subjects were apathetic. Apathy was significantly associated with male gender, higher depression scores and more severe motor symptoms, but was not associated with greater cognitive impairment. When excluding patients with significant depressive symptoms, apathy remained significantly associated with motor severity. Approximately 50% of the caregivers of patients with apathy reported the apathetic behaviour to be at least moderately distressing. The association between apathy and motor severity in our PD cohort suggests a common underlying pathophysiological mechanism. Future studies should explore the longitudinal effect of dopamine replacement therapy on apathetic behaviour in early PD. The relationship between apathy and male gender needs further study to be fully evaluated. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To present the incidence of Parkinson’s disease (PD) in Norway and to explore gender influences on incidence and age at onset, as well as severity and pattern of parkinsonism at the time of diagnosis in a representative drug naïve cohort with newly diagnosed PD. METHODS: In four Norwegian counties comprising a base population of 1 052 075 inhabitants, multiple sources of case ascertainment and a four step diagnostic procedure were used to establish a representative cohort of patients with incident PD at a high level of diagnostic accuracy. Of a total of 604 subjects referred to the study, 265 individuals fulfilled the clinical research criteria of PD at their latest clinical visit, at a mean 28 months after identification. RESULTS: The incidence of PD in the study area, age standardised to the 1991 European standard population, was 12.6/105yr-1(95% CI 11.1 to 14.2). The overall age standardised male to female ratio was 1.58 (95% CI 1.22 to 2.06), with a consistent male preponderance throughout all age groups. Clinical onset of PD was later in women than in men (68.6 vs 66.3 years; p = 0.062) whereas severity and pattern of parkinsonism in drug naïve patients was not different between genders at the time of diagnosis. CONCLUSION: Incidence rates of PD in Norway are similar to those in other Western European and American countries. Female gender was associated with a considerably lower risk of PD and slightly delayed motor onset but had no impact on severity of parkinsonism or clinical phenotype in incident drug naïve PD, suggesting that the female gender influences on the nigrostriatal system are most pronounced in the preclinical phase of the disease. [ABSTRACT FROM AUTHOR]

Background: There is no consensus for the management of incidental meningiomas. The literature on long-term growth dynamics is sparse and the natural history of these tumors remains to be illuminated. Methods: We prospectively assessed long-term tumor growth dynamics and survival rates during active monitoring of 62 patients (45 female, mean age 63.9) harbouring 68 tumors. Clinical and radiological data was obtained every 6 months for two years, then annually. Results: The natural history of incidental meningiomas during 12 years of monitoring was growth (p < 0.001). However, mean growth decelerated and became insignificant at 1.5 years. Self-limiting growth patterns were seen in 43 (63.2 %) tumors, non-self-limiting in 20 (29.4%) and 5 (7.4 %) were indecisive due to ≤ 2 measurements. Decelerating growth persisted once established. During follow-up, 38 (97.4 %) of 39 tumor treatments were initiated within 5 years. None developed symptoms prior to intervention. Tumor volume (p < 0.001) and relation to venous sinuses (p = 0.039) correlated with more aggressive growth. Since inclusion 16 (25 %) patients died of unrelated causes and 2 (3 %) from atypical tumors. Conclusion: Active monitoring seems an optimal first line management for incidental meningiomas. Intervention was avoided in > 40 % with indolent tumors. Nearly all treatments were initiated within five years and were not compromised by tumor growth. Clinical follow-up seems sufficient beyond five years if self-limiting growth is established. Tumors with steady or accelerating growth warrant monitoring until they reach a stable state or treatment is mandatory. [ABSTRACT FROM AUTHOR]

The collapsin response mediator protein 5 (CRMP5) antibody is usually associated with paraneoplastic neurological syndrome (PNS) and small-cell lung cancer (SCLC) or thymoma. The objective of this study was to assess the frequency of CRMP5 antibodies in patients with such tumours and to see if the presence of antibodies was associated with prognosis in these cancers. A multi-well adapted immunoprecipitation assay using radiolabelled recombinant CRMP5 protein, produced by coupled in vitro transcription/translation, was used for the detection of CRMP5 antibodies. Sera from 200 patients with SCLC, 73 patients with thymoma and myasthenia gravis (MG) and from 300 healthy blood donors were examined for CRMP5 antibodies. Positive sera were also examined by immunofluorescence and immune blots. The serological results were compared with disease severity of the patients with thymoma or SCLC. CRMP5 antibodies were detected in 10/200 (5%) of the SCLC, 9/73 (12%) of the thymomas and in 2/300 (0.6%) of the healthy controls by immunoprecipitation. The antibodies were less frequently detected by immunofluorescence or immune blots. There was no significant correlation between CRMP5 antibodies and disease severity. CRMP5 antibodies are more than twice as frequent, and the antibody levels are higher in patients with thymoma and MG than in patients with SCLC. The antibodies are correlated to these tumours, but not to disease severity. [ABSTRACT FROM AUTHOR]

Background Relevant genetic markers for myasthenia gravis (MG) include tumor necrosis factors α and β, Fcγ receptor IIa, and interleukin 10. The corresponding gene products are thought to be involved in MG pathogenesis. Objectives: To investigate whether MG susceptibility correlates with specific combinations of genetic markers and to compare the contribution of each marker. Participants: Forty-seven patients with MG and 92 healthy blood donors. Main Outcome Measures: Presence of tumor necrosis factors α and β, Fcγ receptor IIa, and interleukin 10 genotypes and autoantibodies against nicotinic acetylcholine receptor, titin, and ryanodine receptor. Results: Susceptibility to MG increases with an increasing number of genetic markers in both thymomatous MG and MG with titin antibodies but not in early-onset MG. In thymomatous MG, Fcγ receptor IIa allelic variants seem to be the most important determinant of disease. Conclusion: Specific combinations of allelic variants individually associated with MG synergize in predisposing to thymomatous MG and MG with titin antibodies. [ABSTRACT FROM AUTHOR]

Important progress has been made in our understanding of the cellular and molecular processes underlying the autoimmune neuromuscular transmission (NMT) disorders; myasthenia gravis (MG), Lambert–Eaton myasthenic syndrome (LEMS) and neuromyotonia (peripheral nerve hyperexcitability; Isaacs syndrome). To prepare consensus guidelines for the treatment of the autoimmune NMT disorders. References retrieved from MEDLINE, EMBASE and the Cochrane Library were considered and statements prepared and agreed on by disease experts and a patient representative. The proposed practical treatment guidelines are agreed upon by the Task Force: (i) Anticholinesterase drugs should be the first drug to be given in the management of MG (good practice point). (ii) Plasma exchange is recommended as a short-term treatment in MG, especially in severe cases to induce remission and in preparation for surgery (level B recommendation). (iii) Intravenous immunoglobulin (IvIg) and plasma exchange are equally effective for the treatment of MG exacerbations (level A Recommendation). (iv) For patients with non-thymomatous autoimmune MG, thymectomy (TE) is recommended as an option to increase the probability of remission or improvement (level B recommendation). (v) Once thymoma is diagnosed TE is indicated irrespective of the severity of MG (level A recommendation). (vi) Oral corticosteroids is a first choice drug when immunosuppressive drugs are necessary in MG (good practice point). (vii) In patients where long-term immunosuppression is necessary, azathioprine is recommended together with steroids to allow tapering the steroids to the lowest possible dose whilst maintaining azathioprine (level A recommendation). (viii) 3,4-diaminopyridine is recommended as symptomatic treatment and IvIg has a positive short-term effect in LEMS (good practice point). (ix) All neuromyotonia patients should be treated symptomatically with an anti-epileptic drug that reduces peripheral nerve hyperexcitability (good practice point). (x) Definitive management of paraneoplastic neuromyotonia and LEMS is treatment of the underlying tumour (good practice point). (xi) For immunosuppressive treatment of LEMS and NMT it is reasonable to adopt treatment procedures by analogy with MG (good practice point). [ABSTRACT FROM AUTHOR]

Some myasthenia gravis (MG) patients have antibodies against skeletal muscle antigens in addition to the acetylcholine receptor (AChR). Two major antigens for non-AchR antibodies in MG are the Ca2+ release channel of the sarcoplasmic reticulum, the ryanodine receptor (RyR) and titin, a gigantic filamentous muscle protein essential for muscle structure, function and development. RyR and titin antibodies are found mainly in thymoma MG patients and in a few late-onset MG patients and correlate with a severe MG disease. The presence of titin antibodies, which bind to key regions near the A/I junction and in the central I-band, correlates with myopathy. The immunosuppressant (FK506), which enhances Ca 2+ release from the RyR, seems to have a symptomatic effect on MG patients with RyR antibodies. The RyR antibodies recognize a region near the N-terminus important for channel regulation and inhibit Ca 2+ release in vitro. However, evidence that antibodies against the intracellular antigens RyR and titin are pathogenic in vivo is still missing. [ABSTRACT FROM AUTHOR]

Myasthenia gravis is an autoimmune disease caused, in most cases, by antibodies attaching to the acetylcholine receptor. Some myasthenia gravis patients have antibodies that bind in a cross-striational pattern to skeletal and heart muscle tissue sections (striational antibodies). These antibodies react with epitopes on the muscle proteins titin and ryanodine receptor, are found mainly in sera of patients with thymoma and late-onset myasthenia gravis, and may correlate with myasthenia gravis severity. Their presence may predict an unsatisfactory outcome after thymectomy. The detection of titin and ryanodine receptor antibodies provides more specific clinical information than the immunofluorescent demonstration of striational antibodies. [ABSTRACT FROM AUTHOR]

Background: Myasthenia gravis (MG) is caused by autoantibodies to the acetylcholine receptor (AChR). Non-AChR muscle autoantibodies are present in many MG serum samples, mainly from patients with thymoma or late-onset MG. The exact relationship between MG severity and several non-AChR muscle antibodies is unknown. Objective: To study the correlation between the severity of MG and the concentration of antibodies against striated muscle tissue sections, titin, citric acid antigen, ryanodine receptor, and AChR. Setting: The severity of MG was graded in 146 consecutive patients with MG, and their serum samples were tested for the presence of autoantibodies. Ten patients who were titin antibody positive were observed in longitudinal follow-up. Results: No significant difference was found in MG severity between late-onset and thymoma MG. Titin, citric acid antigen, and ryanodine receptor antibodies occurred significantly more often among patients with severe MG than among patients with less severe disease. Changes in MG severity correlated with changes in titin antibody titer in the individual patient. Titin antibodies showed a better longitudinal correlation with disease severity than the AChR antibodies. Conclusions: Non-AChR muscle autoantibodies occurred more frequently in severe MG regardless of MG subgroup. Thymoma per se does not generate a more severe MG. It may well be the presence of a humoral immune response to non-AChR muscle antigens such as titin, citric acid antigen, and ryanodine receptor that leads to a severe disease, not the presence of thymoma or a late age of onset. These antibodies can serve as important prognostic markers in MG regardless of the presence of thymoma. [ABSTRACT FROM AUTHOR]

Myasthenia gravis (MG) is caused by autoantibodies to the acetylcholine receptor (AChR), but several other muscle autoantibodies have also been identified in patient sera. We studied muscle autoantibodies against AChR, striated muscle tissue sections (SH), titin, citric acid antigen (CA), and ryanodine receptor (RyR) in sera from 146 consecutive MG patients to evaluate whether a single test or several tests together can predict a thymoma. The MG patients were divided into five subgroups; ocular MG, early-onset MG (< 50 years), late-onset MG (≥ 50 years), MG with thymoma, and AChR antibody negative MG. AChR, SH, titin, CA, and RyR antibodies were detected in 85%, 34%, 34%, 25%, and 14% of the MG patients, respectively. For thymoma MG, AChR, SH, titin, CA, and RyR antibodies were detected in 100%, 75%, 95%, 70%, and 70% respectively. SH, titin, CA, RyR antibodies, and computed tomography of the anterior mediastinum have similar sensitivity for thymoma MG. The specificity of RyR, titin, CA, and SH antibodies for thymoma was 70%, 39%, 38%, and 31%, respectively, which is significantly higher for RyR antibodies than for the others. No single muscle antibody assay can predict a thymoma, and a combination of several antibody assays is preferred, although RyR antibody testing alone showed 70% sensitivity and specificity for thymoma MG. SH and CA antibodies provided only little additional information. [ABSTRACT FROM AUTHOR]