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The use of stereotactic radiosurgery (SRS) for brain metastases are increasing. Response assessment is challenging and the clinical significance of radiological response and retreatments are poorly defined. Ninety-seven patients with a total of 406 brain metastases were followed prospectively for 10 years or until death. Volume changes over time and clinical outcome in response to first time SRS and SRS retreatments were analyzed. Tumors grew significantly before (p = 0.004), but shrunk at 1 and 3 months (p = 0.001) following SRS. Four response-patterns of were observed; tumors either continuously reduced in size (A, 62%), pseudo-progressed (PP, B, 13%), temporarily reduced in size (C, 24%), or grew continuously (D, 2%); corresponding to 75% local control (LC) at initial SRS. Predictors for LC were primary cancer site (p = 0.001), tumor volume (p = 0.002) and target cover ratio (p = 0.005). Subsequent SRS for new lesions resulted in 94% LC (87% A) and repeat-SRS for local failures in 80% LC (57% B), predicted by higher prescribed dose, p = 0.001 and p = 0.042, respectively. Overall survival was only 4.5 months if A-response for all lesions, 13.3 months if at least one B-response, 17.1 months if retreated C- or D-response (p < 0.001), (7.5 and 4.7 months if untreated). Quality of life (p = 0.003), steroid use (p = 0.019) and prior whole brain radiotherapy (p = 0.026) were predictors for survival. There are 4 response patterns to SRS predicted by tumor size, primary cancer site, target cover ratio and prescribed dose. Long-term survivors experienced a higher incidence of PP and were more often retreated for new lesions and local failures. The immune response induced by PP seems beneficial but further studies are needed.

Background A major challenge in the follow-up of patients treated with stereotactic radiosurgery (SRS) for brain metastases (BM) is to distinguish pseudoprogression (PP) from tumor recurrence (TR). The aim of the study was to develop a clinical risk assessment score. Methods Follow-up images of 87 of 97 consecutive patients treated with SRS for 348 BM were analyzed. Of these, 100 (28.7%) BM in 48 (53.9%) patients responded with either TR (n = 53, 15%) or PP (n = 47, 14%). Differences between the 2 groups were analyzed and used to develop a risk assessment score (the Bergen Criteria). Results Factors associated with a higher incidence of PP vs. TR were as follows: prior radiation with whole brain radiotherapy or SRS (P = .001), target cover ratio ≥98% (P = .048), BM volume ≤2 cm3 (P = .054), and primary lung cancer vs. other cancer types (P = .084). Based on the presence (0) or absence (1) of these 5 characteristics, the Bergen Criteria was established. A total score 3 points were associated with 84% TR and 16% PP, P < .001. Conclusion Based on 5 characteristics at the time of SRS the Bergen Criteria could robustly differentiate between PP vs. TR following SRS. The score is user-friendly and provides a useful tool to guide the decision making whether to retreat or observe at appropriate follow-up intervals.

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 (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.

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. publishedVersion

There is no consensus for the management of incidental meningiomas. To evaluate the natural history, we assessed tumour growth dynamics during 10 years of active monitoring of 62 patients (45 female and mean age 63.9) harbouring 68 tumours. Radiological and clinical data was obtained was obtained biannually for two years, then annually the following eight. Thirty-six patients (38 tumours) were referred to treatment and/or died of unrelated causes (n=5) within 5 years. The remaining were monitored for up to 10 years. Mean overall survival was at 128 months (95% CI: 118.8-136.7). Median progression free survival was 34 months (95% CI: 14.7-53.3). Median time for growth requiring intervention was 46 months (95% CI: 23.5-68.5). All tumours with self-limiting growth at 5 years (57.9 %) were still stable or reducing in size at 10 years. Mean growth rate decreased from 0.27 cm3/year (95% CI: 0.10-0.43) during the early observation period (0-5 years) to 0.09 cm3/year (95% CI: -0.02-0.21) in the late observation period. No tumours were referred to treatment during the late observation period. Two patients, both with verified WHO2 grade meningiomas succumbed to the disease, seven and eight years after diagnosis. No other patients developed symptoms and none other of the 18 total mortalities were meningioma related. Most clinical and radiological events occur within 5 years after diagnosis. Our findings suggests that if tumour growth slows down during the first 5 years of monitoring, this trend will continue. Clinical follow-up should be sufficient when a self-limiting growth pattern has been established.

Background and purpose Myasthenia gravis (MG) is an autoimmune disease caused by antibody mediated impairment in the neuromuscular junction. Seronegative MG (SNMG) without antibodies against acetylcholine receptor (AChR) and muscle-specific kinase (MuSK) by routine assays accounts for about 20% of all MG patients. Methods Plasma from 81 Chinese MG patients previously found to be seronegative was tested by routine assays for AChR and MuSK antibodies. These samples were screened by (i) a novel, highly sensitive radioimmunoassay for AChR antibodies; (ii) cell-based assays for clustered AChR, MuSK and lipoprotein receptor-related protein 4 (LRP4) antibodies; (iii) a radioimmunoassay for titin antibodies. Results Antibodies to AChR, MuSK, LRP4 and titin were found in 25% (20/81), 4% (3/81), 7% (6/81) and 6% (5/78) of SNMG patients, respectively. In total, 37% of SNMG patients were found to be positive for at least one of the tested antibodies. AChR antibody positive patients had more severe disease (P = 0.008) and a trend towards fewer remissions/minimal manifestations than AChR antibody negative patients. The four patients with coexistence of antibodies had more severe disease, whilst the seronegative patients had milder MG (P = 0.015). Conclusions Detection of multiple muscle antibodies by more sensitive assays provides additional information in diagnosing and subgrouping of MG and may guide MG treatment.

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

Source at https://doi.org/10.3389/fnhum.2019.00177. 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.

Source at https://doi.org/10.1038/s41598-019-48791-0. © The Author(s) 2019 Persons with Parkinson’s disease have general timing deficits and have difficulties in rhythm discrimination tasks. The basal ganglia, a crucial part of Parkinson’s disease pathology, is believed to play an important role in rhythm and beat processing, with a possible modulation of basal ganglia activity by level of rhythmic complexity. As dysfunction in basal ganglia impacts function in other brain areas in Parkinson’s disease during temporal processing, investigating the neuronal basis for rhythm processing is important as it could shed light on the nature of basal ganglia dysfunction and compensatory mechanisms. We constructed an auditory beat-omission fMRI paradigm with two levels of rhythm complexity, to investigate if and where persons with Parkinson’s disease showed abnormal activation during rhythm and omission processing, and whether such activations were modulated by the level of rhythmic complexity. We found no effect of complexity, but found crucial group differences. For the processing of normal rhythm presentations, the Parkinson-group showed higher bilateral planum temporal activity, an area previously associated with the processing of complex patterns. For the omissions, the Parkinson-group showed higher activity in an area in the right superior temporal gyrus previously associated with detection of auditory omissions. We believe this shows a pattern of “hypersensitive” activity, indicative of task-specific, compensatory mechanisms in the processing of temporal auditory information in persons with Parkinson’s disease.

Source at https://doi.org/10.1002/hbm.24421. 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.

A major challenge in the follow-up of patients managed with stereotactic radiosurgery (SRS) brain for metastases (BM) is to differentiate pseudoprogression (PP) from tumor recurrence (TR). A clinical score based on tumor and treatment related factors would be valuable when selecting appropriate treatment. Follow-up images of 97 consecutive patients treated with SRS for 406 BM were analyzed. We included 100 (24.6 %) BM in 42 (43.3 %) patients which responded either with TR (delayed growth; 53 (13.1 %) BM in 27 patients) or PP (temporary volume increase; 47 (11.6 %) BM in 15 patients). Differences between the 2 groups were analyzed and used to develop a PP risk assessment score (PP-RAS). Significant factors associated with a higher incidence of PP versus TR were: primary lung cancer vs. other primaries, BM volume < 2cc (or BM < 1.5 cm in diameter), Target cover ratio ≥ 98 % and prior radiation with SRS or WBRT. Based on the presence (0) or not (1) of these 5 parameters, a risk assessment score for PP versus TR was established. A PP-RAS score of 0 corresponds with high risk of PP vs.TR, whereas a score of 5 corresponds low risk of PP vs. TR. A score of ≤ 1 point was associated with 100 % PP, 2 points with 57 % PP and 43 % TR, 3 points with 57 % TR and 43 % PP whereas ≥ 4 points were associated with 84 % TR and 16 % PP, π=24.57, df =4, p < 0.001). Based on these 5 parameters at the time of SRS our risk assessment score could robustly differentiate between PP versus growth following SRS. The score is user-friendly and may be a useful tool to guide the decision making whether to retreat or observe at appropriate follow-up intervals.

Myasthenia gravis (MG) is an autoimmune disorder with heterogeneity. Antibodies against acetylcholine receptor (AChR), muscle-specific kinase (MuSK), titin and ryanodine receptor (RyR) were examined in 437 adult Chinese MG patients. The AChR, MuSK, titin and RyR antibodies were found in 82.2%, 2.3%, 28.4% and 23.8% of all patients. Autoantibody profiles vary among different MG subgroups. Thymoma MG patients had high frequencies of AChR (99.2%), titin (50.8%) and RyR antibodies (46.9%). The titin and RyR antibodies also showed high frequencies in late onset patients (54.4% and 33.3%, respectively). These two antibodies may indicate an underlying thymoma when combined. The patients with titin and RyR antibodies tend to have more severe disease and worse outcome, and may need more active immunosuppressive treatment.

Myasthenia gravis (MG) is an autoimmune disorder caused by autoantibodies that target the neuromuscular junction, leading to muscle weakness and fatigability. Currently available treatments for the disease include symptomatic pharmacological treatment, immunomodulatory drugs, plasma exchange, thymectomy and supportive therapies. Different autoantibody patterns and clinical manifestations characterize different subgroups of the disease: early-onset MG, late-onset MG, thymoma MG, muscle-specific kinase MG, low-density lipoprotein receptor-related protein 4 MG, seronegative MG, and ocular MG. These subtypes differ in terms of clinical characteristics, disease pathogenesis, prognosis and response to therapies. Patients would, therefore, benefit from treatment that is tailored to their disease subgroup, as well as other possible disease biomarkers, such as antibodies against cytoplasmic muscle proteins. Here, we discuss the different MG subtypes, the sensitivity and specificity of the various antibodies involved in MG for distinguishing between these subtypes, and the value of antibody assays in guiding optimal therapy. An understanding of these elements should be useful in determining how to adapt existing therapies to the requirements of each patient.

OBJECTIVES Myasthenia gravis (MG) represents a spectrum of clinical subtypes with differences in disease mechanisms and treatment response. MG with muscle-specific tyrosine kinase (MuSK) antibodies accounts for 1%-10% of all MG patients. We conducted a meta-analysis to evaluate the association between HLA genes and MuSK-MG susceptibility. SUBJECTS AND METHODS Studies were searched in Pubmed, EMBASE database and other sources between 2001 and 2018. Genotype, allele and haplotype frequencies of HLA loci in MuSK-MG patients and healthy controls were extracted from each included study. RESULTS The meta-analysis showed that HLA DQB1*05, DRB1*14 and DRB1*16 were strongly associated with an increased risk of MuSK-MG (P

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.

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.

Background Hypokalemic pareses are caused by low extracellular potassium levels which reduce the resting membrane potential of muscle cells and make them less excitable. It may be caused by an intracellular shift of potassium, renal potassium loss, reduced potassium intake or increased gastrointestinal loss. Case presentation A woman in her 60s presented with rapid-onset tetraparesis and hyporeflexia starting the day before admission. The patient history revealed several months of low food intake, increased alcohol consumption and diarrhoea. Laboratory tests showed severe hypokalemia (1.5 mmol/l) and hypomagnesemia (0.38 mmol/l), and ECG showed atrial fibrillation. She was admitted to the medical intensive care unit and treated with intravenous normal saline with added potassium and magnesium, with good effect on her symptoms. Urine tests showed high potassium-creatinine ratio (4.22 mmol/mmol creatinine) and increased fractional excretion of magnesium (18.6%). Abdominal CT scan revealed colonic wall thickening, and colonic biopsies showed mild inflammation. Faecal calprotectin was moderately elevated (294 mg/kg). Interpretation The patient had hypokalemic pareses for which there were several contributing factors. The renal causes were augmented excretion of magnesium and potassium, probably due to increased alcohol consumption. The extrarenal causes were increased gastrointestinal loss, with ulcerative colitis being the presumed explanation, and reduced food intake.

OBJECTIVELung cancer (LC) patients who develop brain metastases (BMs) have a poor prognosis. Estimations of survival and risk of treatment-related deterioration in quality of life (QOL) are important when deciding on treatment. Although we know of several prognostic factors for LC patients with BMs, the role of QOL has not been established. Authors of this study set out to evaluate changes in QOL following Gamma Knife surgery (GKS) for BMs in LC patients and QOL as a prognostic factor for survival.METHODSForty-four of 48 consecutive LC patients with BMs underwent GKS in the period from May 2010 to September 2011, and their QOL was prospectively assessed before and 1, 3, 6, 9, and 12 months after GKS by using the Functional Assessment of Cancer Therapy–Brain (FACT-BR) questionnaire. A mixed linear regression model was used to identify potential predictive factors for QOL and to assess the effect of GKS and the disease course on QOL at follow-up.RESULTSMean QOL as measured by the brain cancer subscale (BRCS) of the FACT-BR remained stable from baseline (score 53.0) up to 12 months post-GKS (57.1; p = 0.624). The BRCS score improved for 32 patients (72.3%) with a total BM volume ≤ 5 cm3. Mean improvement in these patients was 0.45 points each month of follow-up, compared to a decline of 0.50 points each month despite GKS treatment in patients with BM volumes > 5 cm3 (p = 0.04). Asymptomatic BMs (p = 0.01), a lower recursive partitioning analysis (RPA) classification (p = 0.04), and a higher Karnofsky Performance Scale (KPS) score (p < 0.01) at baseline were predictors for a high, stable QOL after GKS. After multivariate analysis, a high KPS score (p < 0.01) remained the only positive predictor of a high, stable QOL post-GKS.Median survival post-GKS was 5.6 months (95% CI 1.0–10.3). A higher BRCS score (p = 0.01), higher KPS score (p = 0.01), female sex (p = 0.01), and the absence of liver (p = 0.02), adrenal (p = 0.02), and bone metastases (p = 0.03) predicted longer survival in unadjusted models. However, in multivariate analyses, a higher BRCS score (p < 0.01), female sex (p = 0.01), and the absence of bone metastases (p = 0.02) at GKS remained significant predictors. Finally, the BRCS score’s predictive value for survival was compared with the values for the variables behind well-known prognostic indices: age, KPS score, extracranial disease status, and number and volume of BMs. Both BRCS score (p = 0.01) and BM volume (p = 0.05) remained significant predictors for survival in the final model.CONCLUSIONSPatient-reported QOL according to the BRCS is a predictor of survival in patients with BMs and may be helpful in deciding on the optimal treatment. Gamma Knife surgery is a safe and effective therapeutic modality that improves QOL for LC patients with a BM volume ≤ 5 cm3 at treatment. Careful follow-up and salvage therapy on demand seem to prevent worsening of QOL due to relapse of BMs.

Background Parkinson's disease is a progressive movement disorder recognized by motor symptoms which frequently are measured and longitudinally monitored using the Unified Parkinson Disease Rating Scale (UPDRS). The factor structure of the UPDRS has yet not been analyzed in early PD. Methods A population-based cohort of patients with PD was investigated at the time of diagnosis, one year and three years later. The factor structure of the motor section of the UPDRS was explored using Principal Component Analysis (PCA). Results We found that the factor structure, the interrelatedness among variables, is different in the first year from diagnosis compared to later stages, but evolves at three years to resemble the factor structure reported for more advanced PD. The only consistent factor throughout the observation period was an axial factor. Conclusion The factor structure differs in early versus more advanced PD, but resembles the factor structure of more advanced PD after three years. This is likely due to a higher proportion of subjects with unilateral motor symptoms in early stages of PD together with a changing distribution of motor symptoms with further disease progression. Initiation of PD medication did not alter the factor structure in early PD. The axial factor was the most consistent factor in early PD and could be the most appropriate factor to monitor progression across the earliest stages of PD.

OBJECTIVE: A major challenge in the follow-up of patients managed with stereotactic radiosurgery (SRS) for brain metastases (BM) is to differentiate pseudoprogression (PP) from tumor recurrence (TR). A clinical score based on tumor and treatment related factors would be valuable when selecting appropriate treatment. MATERIAL AND METHODS: Follow-up images of 97 consecutive patients treated with SRS for 406 BM were analyzed. Of these 100 (24.6 %) BM in 48 (49.5 %) patients responded either with TR (delayed growth; 53 (13.1 %) BM) or PP (temporary volume increase; 47 (11.6 %) BM). Differences between the 2 groups were analyzed and used to develop a PP risk assessment score (PP-RAS). RESULTS: Significant factors associated with a higher incidence of PP versus TR were: primary lung cancer vs. other primaries, BM volume ≤ 2cc (or BM ≤ 1.5 cm in diameter), Target cover ratio > 98 % and prior radiation SRS or WBRT. Based on the presence (0) or not (1) of these 5 parameters, a risk assessment score for PP versus TR was established. A PP-RAS score of 0 corresponds with high likelihood of PP vs. TR, whereas a score of 5 corresponds with a high risk of TR. A score of ≤ 1 point was associated with 100 % PP, 2 points with 57 % PP and 43 % TR, 3 points with 57 % TR and 43 % PP, whereas ≥ 4 points were associated with 84 % TR and 16 % PP, π=24.57, df =4, p < 0.001). CONCLUSION: Based on these 5 parameters at the time of SRS our risk assessment score could robustly differentiate between PP versus growth following SRS. The score is user-friendly and may be a useful tool to guide the decision making whether to retreat or observe at appropriate follow-up intervals.

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.

There are few reports on the effect of gamma knife surgery (GKS) for brain metastases from colorectal cancer. The purpose of this study was to identify prognostic factors for local control, complications, and survival in our series of patients treated with GKS.Eighty patients (36 males, 44 females) with 140 metastases who received GKS between 1996 and 2008 were retrospectively reviewed. The mean tumor volume was 6.13 (0.01-35.5) cm(3); the prescription dose was 21.1 (10-25.1) Gy and the maximum dose 42.7 (17.2-66.7) Gy; and the tumor cover was 95.0% (72%-100%).Growth control was achieved in 93 of 121 tumors (76.9%) and 42 of 68 (61.8%) patients, while treatment failure was seen in 28 of 121 tumors (23.1%). Local control was better if a high prescription dose of 25 Gy was used, 88.4% vs. 71.4% (P = 0.017), or if tumor volume was5 cm(3) (86.4%), compared with 69.9% for 5-20 cm(3) and 51.9% for20 cm(3) (P = 0.002). The hazard ratio for local failure with lower prescription doses was 2.8 (P = 0.026) in the unadjusted, and 8.5 (P = 0.055) in the adjusted multivariate analysis (tumor volumes5 cm(3)). The median survival was 6 months (range 0-75) after GKS. Age70 years (P0.001) and high RPA class (P = 0.032) were associated with longer survival. Fifteen patients (22.1%) had persistent edema on follow-up MRI, possibly because of radiation damage to the tumor. Radiation-induced edema was asymptomatic in 93.8%. We found neither a decrease in the incidence of new metastases nor improved survival when whole-brain radiation therapy was given prior to GKS.GKS provides reasonable local tumor control. Local control rate is highest if the margin dose is 25 Gy and the tumor volume5 cm(3). Radiation edema was common but rarely symptomatic. Survival is longest for young, well-functioning patients.

Objectives There are limited data on treatment effect in early and drug-naive 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-naive patients from a longitudinal cohort (The Norwegian ParkWest 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.

We report four cases of focal myositis. The patients, three men and one woman, had painful muscle hypertrophy, affecting four different sites. MRI confirmed the muscle enlargement and oedema. Electromyography revealed evidence of acute and chronic denervation in all four cases. Muscle biopsy was available in three and confirmed features suggestive of focal myositis. Based on our patient material, we suggest that chronic nerve irritation, such as compression, can lead to muscle hypertrophy which, when prolonged, provokes fibre necrosis and secondary inflammation. Our finding in four patients having hypertrophy involving four different sites, leads us further to suggest that this may be the common mechanism behind focal myositis.

The aim was to examine potential joint disease mechanisms for myasthenia gravis (MG) and amyotrophic lateral sclerosis (ALS) through the examination of long-term patient cohorts for comorbidity. Recent studies support early involvement of the neuromuscular junction in ALS patients with subsequent degeneration of motor neurons. Medical records at Haukeland University Hospital from 1987 to 2012 were examined for International Classification of Diseases diagnostic codes for MG and ALS. Sera were re-tested for antibodies to acetylcholine receptor, titin, MuSK and GM1. We report one patient with both MG and ALS, and another 3 patients with suggestive evidence of both conditions. This is far more than expected from prevalence and incidence figures in this area if the disorders were unrelated. Our data suggest that immunological mechanisms in the neuromuscular junction are relevant in ALS pathogenesis. Attention should be given to possible therapeutic targets in the neuromuscular junction and muscle in ALS patients.

Introduction: Myasthenia gravis (MG) is an autoimmune disease. Patients without detectable antibodies against the nicotinic acetylcholine receptor or the muscle-specific tyrosine kinase are referred to as seronegative MG (SNMG). Because late-onset congenital myasthenic syndromes (CMSs) due to RAPSN or DOK7 mutations may be mistaken for SNMG, we investigated their frequency in a nationwide SNMG cohort. Methods: We performed sequencing of RAPSN and DOK7 in all Norwegian SNMG patients (n = 74) and 37 healthy controls, examining for the N88K and c.1124_1127dupTGCC mutations, respectively. Results: We found 1 patient homozygous for N88K and 2 carriers of the N88K mutation. Sequencing of DOK7 revealed no mutations. Conclusions: This study confirms that rapsn CMS can be mistaken for SNMG. In addition, the frequency of rapsn CMS in our nationwide SNMG cohort was found to be low. SNMG patients with an atypical clinical presentation and pediatric cases should be tested for the N88K mutation before initiation of immunosuppressive drug treatment or thymectomy. Muscle Nerve, 2011

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.

Although nonmotor symptoms are increasingly recognized as key features in Parkinson's disease (PD), the occurrence and severity of autonomic and sensory symptoms in patients with very early and untreated PD are poorly documented. Two hundred seven patients with newly diagnosed, untreated PD and 175 controls from the population-based Norwegian ParkWest study were included. Postural blood pressure and olfactory function were measured and eight autonomic and sensory symptoms assessed using interview-based rating scales. Autonomic and sensory symptoms were more frequent in patients compared with controls (mean number of symptoms 2.9 vs. 1.1; P < 0.001) and in the postural instability and gait difficulty motor-subtype vs. tremor dominant subtype (mean 3.3 vs. 2.5; P = 0.008). In the patient group, reduced olfaction (59%), urinary problems (47%), increased saliva or drooling (42%), constipation (39%), and sensory complaints (34%) were the most frequent symptoms. Daily activities were not affected by these symptoms in 58% of the patients, and the influence on daily activities was rated as "mild" or less for all of these symptoms in 90%. A higher Hoehn and Yahr stage was associated with a higher number of autonomic and sensory symptoms and with the occurrence of gastrointestinal symptoms. Autonomic and sensory symptoms are common in patients with untreated, early PD although the severity of these symptoms is mild, with little or no influence on daily activities. The high prevalence of increased saliva or drooling close to the time of diagnosis is noteworthy and not described earlier.

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.

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).

OBJECTIVE: Resection of meningiomas involving the cavernous sinus often is incomplete and associated with considerable morbidity. As a result, an increasing number of patients with such tumors have been treated with gamma knife surgery (GKS). However, few studies have investigated the long-term outcome for this group of patients. METHODS: 100 patients (23 male/77 female) with meningiomas involving the cavernous sinus received GKS at the Department of Neurosurgery at Haukeland University Hospital, Bergen, Norway, between November 1988 and July 2006. They were followed for a mean of 82.0 (range, 0-243) months. Only 2 patients were lost to long-term follow-up. Sixty patients underwent craniotomy before radiosurgery, whereas radiosurgery was the primary treatment for 40 patients. RESULTS: Tumor growth control was achieved in 84.0% of patients. Twelve patients required re-treatment: craniotomy (7), radiosurgery (1), or both (4). Three out of 5 patients with repeated radiosurgery demonstrated secondary tumor growth control. Excluding atypical meningiomas, the growth control rate was 90.4%. The 1-, 5-, and 10-year actuarial tumor growth control rates are 98.9%, 94.2%, and 91.6%, respectively. Treatment failure was preceded by clinical symptoms in 14 of 15 patients. Most tumor growths appeared within 2.5 years. Only one third grew later (range, 6-20 yr). The complication rate was 6.0%: optic neuropathy (2), pituitary dysfunction (3), worsening of diplopia (1), and radiation edema (1). Mortality was 0. At last follow-up, 88.0% were able to live independent lives. CONCLUSION: GKS gives long-term growth control and has a low complication rate. Most tumor growths manifest within 3 years following treatment. However, some appear late, emphasizing the need for long-term follow-up.

The prevalence of myasthenia gravis (MG) in people over 50 years of age is increasing, mainly because of the increase in the percentage of people aged 65 years and over in society. The clinical symptoms are the same as in early onset, but may be more difficult to detect in the elderly. Most MG patients with symptom onset after 50 years of age have thymic atrophy. Approximately 10–15% of all patients with MG have a thymoma. Antibodies to non-acetylcholine receptors, such as titin and the ryanodine receptor, are common in early-onset MG thymoma, and more than 40% of patients with late-onset MG have such antibodies. The outcome after thymectomy in MG is generally less favorable in patients over 45 years of age. Standard nonsurgical therapy for late-onset MG follows a similar pattern as for early onset.

Paraneoplastic myasthenia gravis (MG) is accompanied by a neoplasm, usually thymoma. In patients with thymoma and a specific genetic make-up, the paraneoplastic immune response develops further in thymic remnant or peripheral lymphatic tissue. Paraneoplastic MG and late-onset MG (age >or= 50 years) share a similar immunological profile with high titin and ryanodine receptor (RyR) antibody prevalence. This profile is the most important predictor of clinical outcome in paraneoplastic MG. The presence of a thymoma per se does not cause more severe MG. MG severity is linked to the patient's immunological profile. Paraneoplastic MG causes a distinctive non-limb symptom profile at MG onset, characterized by bulbar, ocular, neck, and respiratory symptoms. When the diagnosis of paraneoplastic MG is established, the neoplasm should be removed surgically. Pre-thymectomy plasmapheresis or iv-IgG should be considered in these patients to minimize post-thymectomy MG exacerbation risk. Paraneoplastic MG usually continues after thymectomy. The pharmacological treatment of paraneoplastic MG does not differ from non-paraneoplastic MG, except for tacrolimus that should be considered in difficult cases. Tacrolimus is an immunosuppressant acting specifically in RyR antibody positive patients through enhancing RyR-related sarcoplasmic calcium release that in theory might be blocked by RyR antibodies, causing symptomatic relief in paraneoplastic MG.

Of sera of patients with myasthenia gravis (MG), 30% contains titin and ryanodine receptor (RyR) antibodies. In early-onset MG (i.e., before 50 years of age), the presence of titin antibodies strongly suggests a thymoma. Late-onset MG comprises one MG group, characterized by a broad antimuscle immune response, including both titin and the acetylcholine receptor (AChR). Another group is preferentially associated with the HLA-A3, B7 and DRw2 antigens, representing a delayed early-onset of the disease that has a selective AChR immune response. The presence of titin and RyR antibodies is associated with more severe disease. Titin antibodies may, in some patients with rippling muscle disease, affect the contractile machinery of myofibers, thereby affecting their mechanical sensitivity. It is not known whether this occurs in MG. RyR antibodies may impair excitation–contraction coupling and contribute to muscle weakness in MG patients. Titin antibodies may serve as tumor markers in early-onset MG patients.

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.

Parkinson's disease (PD) may be associated with a number of different diseases due to common risk factors or overlapping symptomatology. We have asked for possible associated disorders in a Norwegian population of incident PD patients and controls, the Norwegian ParkWest study. The patients were diagnosed according to the Gelb criteria. 212 incident PD patients and 175 age and gender matched controls were included. PD patients and controls were asked for information on earlier medical history and family history. PD patients had a higher frequency of self-reported symptoms of depression (p = 0.003) and anxiety disorders (p = 0.004) before baseline. They tended to have a higher frequency of diabetes (p = 0.09) and had a higher frequency of prior stroke or TIA (p = 0.004).

Myasthenia gravis (MG) in individuals over 40 years of age comprises three groups: early-onset MG with prolonged disease duration, late-onset MG with thymoma, and late-onset of nonthymomatous MG. The clinical features do not differ between the three groups, except that early-onset patients with prolonged disease duration usually have a less severe disease. More than 60% of our MG patients are now more than 50 years of age, often with disease onset after age 40. Although 2 out of the 3 patients in Erb's original description had onset of myasthenic symptoms after age 40, this was apparently infrequent in 1879, when the disease was first identified. Onset of MG after age 40 is now common. For example, in our material, 88/184 (47.8%) had onset of MG after age 40. Eighteen (20.5%) had a thymoma. The female:male ratio in the early-onset group was 2.4:1, whereas it was 1:1.1 among those with onset after age 40. There was no human leukocyte antigen association for MG with thymoma. Antibodies to the acetylcholine receptor were detected in 88% of sera from nonthymomatous MG and in 100% of those with late-onset MG with thymoma. Antibodies to titin were found in sera from 85.7% of MG patients with thymoma (all age groups) and in 58% of nonthymomatous MG with late onset and acetylcholine receptor antibodies. Late-onset, nonthymomatous MG comprises two subgroups, one corresponding to delayed early onset and one immunologically similar to that seen in patients with MG and thymoma.

Some myasthenia gravis (MG) patients have antibodies against non-acetylcholine receptor (AChR) epitopes of skeletal muscle including titin. Peripheral blood lymphocytes from 11 MG patients and 13 blood-donors were tested for lymphocyte proliferation after stimulation with the titin peptide MGT-30, which represents the main immunogenic region. Four out of seven titin antibody positive patients had significant stimulation defined as a stimulation index (SI) above 2. Neither of the four titin antibody negative patients nor the 13 blood-donors had SI above 2 (p = 0.001). Mean SI was significantly higher for T-cells from titin antibody positive MG patients, SI = 2.2 ± 0.8, compared to titin antibody negative patients, SI = 0.9 ± 0.2 (p = 0.01), and blood-donors, SI = 0.8 ±0.3 (p > 0.0005). After MGT-30 stimulation, IL-4 was detected in the blood lymphocyte culture supernatant from four of the five MG patients examined, but from none of the eight blood-donors. Thus, MG patients with anti-titin antibodies have a T-cell mediated immune reaction against titin.

Twenty-two late-onset, non-thymoma myasthenia gravis (MG) patients were selected for study based on the combined presence of MG and involution of the thymus. Thymectomy specimens from all the patients were examined histologically and immunohistologically and compared with an age-matched control group in which tissue was removed from the thymic gland during operations for various cardiac conditions. We were not able to find any morphological differences between thymi from MG patients and patients in the control group. Germinal centres were present in 7/22 in the patient group and 6/20 in the control group. Seven of our 22 MG patients had auto-antibodies to titin. Germinal centres in the thymus were found in only one. In contrast germinal centres were present in the thymus of 6/15 MG patients with no detectable antibody response to titin (p= 0.01). Our study suggests that late-onset MG is pathogenetically heterogeneic with different modes of auto-sensitisation.

Myasthenia gravis (MG) patients may have circulating autoantibodies against titin. In this study, we have stimulated T cells from MG patients with a recombinant polypeptide containing the main immunogenic region of titin, MGT-30 (myasthenia gravis titin-30 kDa). In an ELISpot assay, MGT-30 reactive interferon (IFN)-gamma secreting cells (Th1 cells) were detected in six of 10 titin antibody positive MG patients. Such cells were not detected in any of the five titin antibody negative MG patients or in the seven blood donors. In three patients, the stimulated number of cells decreased when total remission of MG symptoms was achieved after thymectomy or following a period of intensive immunosuppressive medication. We detected MGT-30 interleukin (IL)-4 secreting cells (Th2 cells) in two of five titin antibody positive MG patients, but not in the two titin antibody negative patients or the five blood donors examined. We conclude that titin antibody positive MG patients have a combined Th1/Th2 cell mediated immunity against the muscle protein titin.

Sera from 32 thymoma patients, 29 of them with myasthenia gravis (MG), were tested for the presence of circulating antibodies to the ryanodine receptor (RyR) in Western blot RyR is a channel protein essential for the excitation-contraction coupling in skeletal muscle. MG severity was scored according to the Osserman classification during 1–17 years of follow-up (mean 7 years). Fifteen patients (14 MG and 1 non-MG) were RyR-antibody positive. RyR-positive patients had a significantly higher frequency of invasive thymomas (p = 0.01), and also a more severe MG than RyR-antibody negative patients (p = 0.04). The use of immunosuppressive drugs at latest follow-up was more frequent in RyR-antibody positive than in RyR-antibody negative patients (p = 0.02). Thus the presence of RyR-antibodies in thymoma patients is associated with a more severe disease and can be used as a prognostic marker.

Objective To review a series of patients who underwent Gamma Knife surgery (GKS) to identify prognostic factors for local growth control and survival. Methods During the period 1996–2006, 77 patients (42 men and 35 women) with a total of 143 metastases underwent GKS. A solitary lesion was present in 40 patients (51.9%). Results Growth control was achieved in 114 of 128 (89.1%) tumors and 59 of 70 (84.3%) patients. The median survival was 7 months (range 0–73 months) after GKS and 67 months (range 4–327 months) from the time of diagnosis. Patients with absence of extracranial disease lived longer than patients with more widespread disease—median 16 months (range 3–52 months) versus 6 months (range 0–73 months; P = 0.014). A total tumor volume of less than 5 cc was associated with longer survival ( P = 0.041). Survival was significantly longer in recursive partitioning analysis (RPA) class 1 (22 months) than RPA class 2 (7 months) and RPA class 3 (3 months; P = 0.008). Even in cases of treatment failure with tumor growth or appearance of new metastases, GKS slowed down the cerebral disease with no significant reduction in the duration of survival. Conclusions GKS for melanoma brain metastasis provides a high rate of local tumor control. Survival is longest for well-functioning patients with absence of extracranial metastases or with an intracerebral total tumor volume less than 5 cc.

Background The aim of this study was to evaluate characteristics and long-term outcome of young patients with ischemic stroke (15-49 years at stroke onset) and aphasia. Methods Aphasia was defined as less than 10 points in the speech subscale of the Scandinavian Stroke Scale on long-term follow-up. Risk factors, origin, complications, social factors, and the Nottingham Health Profile subscores were compared between aphasic and nonaphasic young patients with ischemic stroke. On long-term follow-up, patients with aphasia were invited for further assessment of severity and subtype of aphasia. Results The study comprised 195 patients still alive after a mean follow-up of 6 years. Twenty (10.3%) patients had aphasia. Aphasia was associated with cardiac embolism ( P = .007), myocardial infarction ( P = .005), epilepsy ( P P = .021), and social isolation ( P = .054). On follow-up, 13 patients with aphasia underwent further assessment. These patients had all improved into milder aphasia subtypes. Conclusion Our study suggests that relatively few young patients with ischemic stroke have clinically significant aphasia on long-term follow-up. However, there are clinically significant differences between patients with and without aphasia that should be the focus of future research.

We studied 65 patients with myasthenia gravis (MG). Clinical, neurophysiological, immunological, and histological findings suggested the coexistence of a presumed autoimmune myopathy. The clinical features were persistent pyridostigmine-resistant weakness and atrophy of striated muscles. The myopathy was found more often in patients with late-onset MG than in those with early-onset (37% vs 13%). Patients with myopathy were also prone to have other immune disorders (47% vs 13%). Elevated titres of antibodies against titin were detected more often in patients with electromyography (EMG) evidence of myopathy than in the sera of those without, and only in late-onset MG cases.