Abnormal phasic activity in saliency network, motor areas, and basal ganglia in Parkinson's disease during rhythm perception.

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.

Neuronal complex I deficiency occurs throughout the Parkinson's disease brain, but is not associated with neurodegeneration or mitochondrial DNA damage.

Mitochondrial complex I deficiency occurs in the substantia nigra of individuals with Parkinson's disease. It is generally believed that this phenomenon is caused by accumulating mitochondrial DNA damage in neurons and that it contributes to the process of neurodegeneration. We hypothesized that if these theories are correct, complex I deficiency should extend beyond the substantia nigra to other affected brain regions in Parkinson's disease and correlate tightly with neuronal mitochondrial DNA damage. To test our hypothesis, we employed a combination of semiquantitative immunohistochemical analyses, Western blot and activity measurements, to assess complex I quantity and function in multiple brain regions from an extensively characterized population-based cohort of idiopathic Parkinson's disease (n = 18) and gender and age matched healthy controls (n = 11). Mitochondrial DNA was assessed in single neurons from the same areas by real-time PCR. Immunohistochemistry showed that neuronal complex I deficiency occurs throughout the Parkinson's disease brain, including areas spared by the neurodegenerative process such as the cerebellum. Activity measurements in brain homogenate confirmed a moderate decrease of complex I function, whereas Western blot was less sensitive, detecting only a mild reduction, which did not reach statistical significance at the group level. With the exception of the substantia nigra, neuronal complex I loss showed no correlation with the load of somatic mitochondrial DNA damage. Interestingly, α-synuclein aggregation was less common in complex I deficient neurons in the substantia nigra. We show that neuronal complex I deficiency is a widespread phenomenon in the Parkinson's disease brain which, contrary to mainstream theory, does not follow the anatomical distribution of neurodegeneration and is not associated with the neuronal load of mitochondrial DNA mutation. Our findings suggest that complex I deficiency in Parkinson's disease can occur independently of mitochondrial DNA damage and may not have a pathogenic role in the neurodegenerative process.

Hyposmia in a simple smell test is associated with accelerated cognitive decline in early Parkinson's disease.

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.

Effects of music production on cortical plasticity within cognitive rehabilitation of patients with mild traumatic brain injury.

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.

Familial aggregation of Parkinson's disease may affect progression of motor symptoms and dementia.

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.

[A woman with pareses of the arms and legs]. / En kvinne med kraftsvikt i armer og bein.

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.

The STRAT-PARK cohort: A personalized initiative to stratify Parkinson's disease.

The STRAT-PARK initiative aims to provide a platform for stratifying Parkinson's disease (PD) into biological subtypes, using a bottom-up, multidisciplinary biomarker-based and data-driven approach. PD is a heterogeneous entity, exhibiting high interindividual clinicopathological variability. This diversity suggests that PD may encompass multiple distinct biological entities, each driven by different molecular mechanisms. Molecular stratification and identification of disease subtypes is therefore a key priority for understanding and treating PD. STRAT-PARK is a multi-center longitudinal cohort aiming to recruit a total of 2000 individuals with PD and neurologically healthy controls from Norway and Canada, for the purpose of identifying molecular disease subtypes. Clinical assessment is performed annually, whereas biosampling, imaging, and digital and neurophysiological phenotyping occur every second year. The unique feature of STRAT-PARK is the diversity of collected biological material, including muscle biopsies and platelets, tissues particularly useful for mitochondrial biomarker research. Recruitment rate is ∼150 participants per year. By March 2023, 252 participants were included, comprising 204 cases and 48 controls. STRAT-PARK is a powerful stratification initiative anticipated to become a global research resource, contributing to personalized care in PD.

Growth dynamics of incidental meningiomas: A prospective long-term follow-up study.

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.

NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson's disease.

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.

The effect of group music therapy on mood, speech, and singing in individuals with Parkinson's disease--a feasibility study.

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.

The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease.

We conducted a double-blinded phase I clinical trial to establish whether nicotinamide adenine dinucleotide (NAD) replenishment therapy, via oral intake of nicotinamide riboside (NR), is safe, augments cerebral NAD levels, and impacts cerebral metabolism in Parkinson's disease (PD). Thirty newly diagnosed, treatment-naive patients received 1,000 mg NR or placebo for 30 days. NR treatment was well tolerated and led to a significant, but variable, increase in cerebral NAD levels-measured by 31phosphorous magnetic resonance spectroscopy-and related metabolites in the cerebrospinal fluid. NR recipients showing increased brain NAD levels exhibited altered cerebral metabolism, measured by 18fluoro-deoxyglucose positron emission tomography, and this was associated with mild clinical improvement. NR augmented the NAD metabolome and induced transcriptional upregulation of processes related to mitochondrial, lysosomal, and proteasomal function in blood cells and/or skeletal muscle. Furthermore, NR decreased the levels of inflammatory cytokines in serum and cerebrospinal fluid. Our findings nominate NR as a potential neuroprotective therapy for PD, warranting further investigation in larger trials.

Autonomic and sensory symptoms and signs in incident, untreated Parkinson's disease: frequent but mild.

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.

Investigation for RAPSN and DOK-7 mutations in a cohort of seronegative myasthenia gravis 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.

A simple score to estimate the likelihood of pseudoprogression vs. recurrence following stereotactic radiosurgery for brain metastases: The Bergen Criteria.

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 <2 points was associated with 100% PP, 2 points with 57% PP and 43% TR, 3 points with 57% TR and 43% PP, whereas >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.

Aphasia among young patients with ischemic stroke on long-term follow-up.

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 < .001), loss of employment (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.

Subjective judgments of rhythmic complexity in Parkinson's disease: Higher baseline, preserved relative ability, and modulated by tempo.

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.

Compensatory task-specific hypersensitivity in bilateral planum temporale and right superior temporal gyrus during auditory rhythm and omission processing in Parkinson's disease.

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.

Neuroplastic Effects in Patients With Traumatic Brain Injury After Music-Supported Therapy.

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.

A prospective study of the natural history of incidental meningioma-Hold your horses!

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.

Retraction Note to: Juvenile-onset myasthenia gravis: autoantibody status, clinical characteristics and genetic polymorphisms.

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.