Biological factors and age-dependence of primary motor cortex experimental plasticity

To evaluate whether the age-dependence of brain plasticity correlates with the levels of proteins involved in hormone and brain functions we executed a paired associative stimulation (PAS) protocol and blood tests. We measured the PAS-induced plasticity in the primary motor cortex. Blood levels of the brain-derived neurotrophic factor (BDNF), estradiol, the insulin-like growth factor (IGF)-1, the insulin-like growth factor binding protein (IGFBP)-3, progesterone, sex hormone-binding globulin (SHBG), testosterone, and the transforming growth factor beta 1 (TGF-β1) were determined in 15 healthy men and 20 healthy women. We observed an age-related reduction of PAS-induced plasticity in females that it is not present in males. In females, PAS-induced plasticity displayed a correlation with testosterone (p = 0.006) that became a trend after the adjustment for the age effect (p = 0.078). In males, IGF-1 showed a nominally significant correlation with the PAS-induced plasticity (p = 0.043). In conclusion, we observed that hormone blood levels (testosterone in females and IGF-1 in males) may be involved in the age-dependence of brain plasticity.     

Parents’ experiences and needs regarding physical and occupational therapy for their young children with cerebral palsy

ObjectiveTo explore the experiences and needs of parents of young children (aged 2–4 years) with cerebral palsy (CP) regarding their child's physical and occupational therapy process in a rehabilitation setting.MethodsA qualitative design was used involving semi-structured interviews with 21 parents of young children with CP. Interviews were conducted until informational redundancy was achieved.ResultsThree major themes were identified: Information, communication and partnership. A fourth, overarching theme emerged: The process of parent empowerment. Experiences and needs differed between parents and changed over time.ConclusionThis study suggests that various themes play a key role in the experiences and needs of parents of young children with CP. The identified themes provide important insights into how and why service providers might change their approach.Practice implicationsBecoming empowered is a dynamic process for parents, in which both parents and service providers play a role. Service providers should continually adapt their role to parents’ needs of information, communication and partnership, and they should support and facilitate parents in becoming empowered. For that, service providers should be educated on the process of parent empowerment, on ways to facilitate this process and on the importance of involving and interacting with parents.This allows families of young children with CP to be provided with services that best suit their needs.     

The therapeutic potential of insulin-like growth factor-1 in central nervous system disorders

Central nervous system (CNS) development is a finely tuned process that relies on multiple factors and intricate pathways to ensure proper neuronal differentiation, maturation, and connectivity. Disruption of this process can cause significant impairments in CNS functioning and lead to debilitating disorders that impact motor and language skills, behavior, and cognitive functioning. Recent studies focused on understanding the underlying cellular mechanisms of neurodevelopmental disorders have identified a crucial role for insulin-like growth factor-1 (IGF-1) in normal CNS development. Work in model systems has demonstrated rescue of pathophysiological and behavioral abnormalities when IGF-1 is administered, and several clinical studies have shown promise of efficacy in disorders of the CNS, including autism spectrum disorder (ASD). In this review, we explore the molecular pathways and downstream effects of IGF-1 and summarize the results of completed and ongoing pre-clinical and clinical trials using IGF-1 as a pharmacologic intervention in various CNS disorders. This aim of this review is to provide evidence for the potential of IGF-1 as a treatment for neurodevelopmental disorders and ASD.     

Elucidation of the anatomy of a satiety network: Focus on connectivity of the parabrachial nucleus in the adult rat

We hypothesized that brain regions showing neuronal activation after refeeding comprise major nodes in a satiety network, and tested this hypothesis with two sets of experiments. Detailed c‐Fos mapping comparing fasted and refed rats was performed to identify candidate nodes of the satiety network. In addition to well‐known feeding‐related brain regions such as the arcuate, dorsomedial, and paraventricular hypothalamic nuclei, lateral hypothalamic area, parabrachial nucleus (PB), nucleus of the solitary tract and central amygdalar nucleus, other refeeding activated regions were also identified, such as the parastrial and parasubthalamic nuclei. To begin to understand the connectivity of the satiety network, the interconnectivity of PB with other refeeding‐activated neuronal groups was studied following administration of anterograde or retrograde tracers into the PB. After allowing for tracer transport time, the animals were fasted and then refed before sacrifice. Refeeding‐activated neurons that project to the PB were found in the agranular insular area; bed nuclei of terminal stria; anterior hypothalamic area; arcuate, paraventricular, and dorsomedial hypothalamic nuclei; lateral hypothalamic area; parasubthalamic nucleus; central amygdalar nucleus; area postrema; and nucleus of the solitary tract. Axons originating from the PB were observed to closely associate with refeeding‐activated neurons in the agranular insular area; bed nuclei of terminal stria; anterior hypothalamus; paraventricular, arcuate, and dorsomedial hypothalamic nuclei; lateral hypothalamic area; central amygdalar nucleus; parasubthalamic nucleus; ventral posterior thalamic nucleus; area postrema; and nucleus of the solitary tract. These data indicate that the PB has bidirectional connections with most refeeding‐activated neuronal groups, suggesting that short‐loop feedback circuits exist in this satiety network. J. Comp. Neurol. 524:2803–2827, 2016. © 2016 Wiley Periodicals, Inc.     

The generational gap: Mental disorder prevalence and disability amongst first and second generation immigrants in Australia

Despite unprecedented numbers of migrants internationally, little is known about the mental health needs of immigrant groups residing in common countries of resettlement. The majority of studies support the ‘healthy migrant hypothesis’, but few studies have examined: 1) shifts in prevalence patterns across generations; 2) how prevalence relates to disability in immigrant groups. Our study examined the prevalence of common mental disorders and disability in first and second generation migrants to Australia. Twelve-month and lifetime prevalence rates of affective, anxiety, and substance use disorders were obtained from the Australian National Survey of Mental Health and Wellbeing (N = 8841). First generation immigrants (born overseas) and second generation immigrants (both parents overseas) from non-English and English speaking backgrounds were compared to an Australian-born cohort. Disability was indexed by days out of role and the WHO Disability Assessment Schedule (WHODAS12). First generation immigrants with non-English speaking (1G-NE) backgrounds evidenced reduced prevalence of common mental disorders relative to the Australian-born population (adjusted odds ratio 0.5 [95% CI 0.38–0.66]). This lower prevalence was not observed in second generation immigrant cohorts. While overall levels of disability were equal between all groups (p > 0.05), mental health-related disability was elevated in the 1G-NE group relative to the Australian-born group (p = 0.012). The findings challenge the overarching notion of the “healthy migrant” and suggest a dissociation between reduced prevalence and elevated mental health-related disability amongst first generation immigrants with non-English speaking backgrounds. These findings highlight the heterogeneous psychiatric needs of first and second generation immigrants.     

Surgical outcomes in patients with mild symptoms,but severely compressed spinal cord from cervical ossification of the posterior longitudinal ligament

Surgical treatment is indicated in patients with moderate to severe myelopathy from cervical ossification of the posterior longitudinal ligaments (OPLL), but undertaking prophylactic surgery for asymptomatic or mildly symptomatic patients with a severely compressed spinal cord is debatable.Patients with <8 mm space available in the spinal canal on CT scan, were divided into groups I (mild symptoms, Japanese Orthopedic Association (JOA) score range 15–16) and II (moderate to severe symptoms, JOA score <14). Medical charts including operative records were reviewed to obtain preoperative, perioperative, and final postoperative follow-up data.Group I included 24 patients (20 men, mean age 52.42 years), and Group II included 46 patients (33 men, mean age 54.67 years). Compared to Group II, Group I had a shorter preoperative symptom duration (19.21 vs. 38.23 months, p = 0.046) and a more favorable JOA score at final follow-up (p = 0.007). The mean numbers of OPLL-involved segments were similar (Group I 2.96, Group II 3.09; p = 0.773) as were the mean numbers of operated segments (Group I 2.71, Group II 3.35; p = 0.076). Perioperative blood loss, operation duration, and hospital stay duration were significantly more favorable in Group I than in Group II. The numbers of surgery-related complications in the two groups were similar.Early surgical treatment for a favorable neurologic recovery with a low perioperative risk can be recommended in patients with severely compressed spinal cord from cervical OPLL who present with mild arm numbness. Surgery-related complications, however, should be carefully monitored regardless of symptom severity.     

Management and outcome of chordomas in the pediatric population: The Hospital for Sick Children experience and review of the literature

Chordomas are tumors arising from remnants of the embryological notochord, most commonly found in the spheno-occipital, spinal, or sacro-coccygeal areas. They are rare tumors in the pediatric population and are challenging to manage due to their difficult accessibility, proximity to important anatomy and extension into adjacent structures. We report a series of 10 children treated for chordoma at The Hospital for Sick Children focusing on their surgery, adjuvant therapy and long-term outcomes. A retrospective review involving patient charts, radiographic imaging, and pathology slides was performed for 10 chordoma patients during the period from 1987–2015. Important variables, including patient demographics, chordoma location, presentation, imaging characteristics, pathology subtype, treatment options, and long-term outcome were analysed. The series consists of seven girls and three boys with cranial or upper cervical spine chordomas. One patient presented with an extradural left cerebellopontine angle chordoma demonstrating aggressive and dedifferentiated features, which, to our knowledge, has not been previously described in the literature. All patients received surgical resection followed by photon or proton radiotherapy. Four patients with chondroid or atypical pathology also received chemotherapeutic adjuvants. All patients with classical pathology achieved favourable outcome, while the four patients with atypical pathology progressed quickly despite aggressive therapy, suggesting that pathology subtype is a crucial prognostic factor. This study summarizes 30 years of surgical and adjuvant therapy experience in a large academic center for pediatric chordoma patients. Patient outcomes were dependent on pathology subtype, and a multidisciplinary approach involving surgery, radiotherapy, and chemotherapy can be considered on an individual basis.     

Does angiogenesis play a role in the establishment of mesial temporal lobe epilepsy?

Mesial temporal lobe epilepsy (MTLE) is a focal epileptic disorder that is frequently associated with hippocampal sclerosis. This study investigated whether blocking angiogenesis prevents the development of seizures and hippocampal atrophy in the pilocarpine rat model of MTLE. To block angiogenesis, a subset of animals were given sunitinib orally. Continuous video recordings were performed to identify seizures. Brains were then extracted and sectioned, and hippocampal surfaces and angiogenesis were assessed. After a latent period of 6.6 ± 2.6 days, the sham-treated pilocarpine rats presented convulsive seizures, while the pilocarpine rats treated with sunitinib did not develop seizures. Sham-treated pilocarpine rats but not sunitinib-treated pilocarpine rats had significantly smaller hippocampi. Endothelial cell counts in sham-treated pilocarpine rats were significantly greater than in controls and sunitinib-treated pilocarpine rats. Blocking angiogenesis immediately following the initial insult in this animal model prevented thus angiogenesis and hippocampal atrophy and averted the development of clinical seizures.