Brain functional alterations in Type 2 Diabetes – A systematic review of fMRI studies

Type 2 Diabetes (T2DM) is emerging as a major global health issue. T2DM can adversely affect cognition and increase dementia risk. This systematic review aimed to examine the functional brain changes that may underlie cognitive dysfunction in adults with T2DM. Studies were restricted to those which used functional magnetic resonance imaging (fMRI). Nineteen independent studies were identified, mostly comprised of middle aged or older adults. Resting-state studies demonstrated that compared to controls, connectivity of the Default Mode Network (DMN) was reduced and the majority of task-based studies identified reduced activation in T2DM patients in regions relevant to task performance. Abnormalities of low frequency spontaneous brain activity were observed, particularly in visual regions. As most studies demonstrated that alterations in fMRI were related to poorer neuropsychological task performance, these results indicate that functional brain abnormalities in T2DM have consequences for cognition.     

Progressive grey matter alterations in bipolar disorder across the life span – A systematic review

Objectives

To elucidate the relationship between the course of bipolar disorder (BD) and structural brain changes across the life span, we conducted a systematic review of longitudinal imaging studies in adolescent and adult BD patients.

Methods

Eleven studies with 329 BD patients and 277 controls met our PICOS criteria (participants, intervention, comparison, outcome and study design): BD diagnosis based on DSM criteria, natural course of disease, comparison of grey matter changes in BD individuals over ≥1-year interval between scans.

Results

The selected studies yielded heterogeneous findings, partly due to varying patient characteristics, data acquisition and statistical models. Mood episodes were associated with greater grey matter loss in frontal brain regions over time. Brain volume decreased or remained stable in adolescent patients, whereas it increased in healthy adolescents. Adult BD patients showed increased cortical thinning and brain structural decline. In particular, disease onset in adolescence was associated with amygdala volume reduction, which was not reported in adult BD.

Conclusions

The evidence collected suggests that the progression of BD impairs adolescent brain development and accelerates structural brain decline across the lifespan. Age-specific changes in amygdala volume in adolescent BD suggest that reduced amygdala volume is a correlate of early onset BD. Clarifying the role of BD in brain development across the lifespan promises a deeper understanding of the progression of BD patients through different developmental episodes.     

Cerebral venous thrombosis in Behçet’s disease: a systematic review

Behçet’s disease (BD) is a chronic inflammatory multisystem disorder which can involve the central nervous system (CNS). Cerebral venous thrombosis (CVT) is one of its major neurological manifestations. We aimed to review the epidemiologic and clinical features of CVT in patients with BD, as well as the available data on therapeutic interventions and prognosis. Systematic review of all observational studies of BD patients was done. Search strategy included electronic searches of MEDLINE (1966-August 2009). Occurrence of CVT in BD and Neuro-Behçet patients, occurrence of CVT as the inaugural manifestation of BD, clinical and neuro-imaging characteristics of CVT, prothrombotic evaluation, treatment options and prognosis were extracted. A meta-analysis of available results was performed when feasible. Twenty-three studies were included, with 290 cases of CVT in patients with BD. The incidence of CVT per 1,000 person-years was 3 (95% CI: 1–8), being higher in retrospective studies (3.2, 95% CI: 1–10) than in prospective studies (2.7, 95% CI: 1–13). Among patients with neurologic involvement, the incidence rate was 15.1/1,000 person-years. The onset was progressive in 77% of the patients. Intracranial hypertension syndrome was a frequent presentation of CVT in BD. The most frequent sites of occlusion were the superior sagittal and the transverse sinus. Most of the studies did not evaluate the prevalence of prothrombotic disorders. Treated CVT was associated with a good prognosis. CVT is a frequent neurological manifestation of BD. When treated, BD-associated CVT bears a good prognosis. There is insufficient information regarding the role of concomitant prothrombotic disorders and specific treatments.     

Cerebral alterations in a MPTP-mouse model of Parkinson’s disease – an immunocytochemical study

Summary. We investigated the immunohistochemical alterations of neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS), tyrosine hydroxylase (TH), microtuble-associated protein 2a,b (MAP 2), glial fibrillary acidic protein (GFAP), parvalbumin (PV), and dopamine transporter (DAT) in the striatum and substantia nigra following the application of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. TH-, MAP 2- and DAT-immunoreactive cells were decreased gradually in the striatum and substantia nigra from 1 day up to 7 days after MPTP treatment, as well as the reduction of the striatal dopamine, DOPAC and HVA content. The number of GFAP-immunoreactive astrocytes increased gradually in the striatum and substantia nigra from 1 day up to 7 days after MPTP treatment. Striatal nNOS-immunoreactive cells were unchanged in MPTP-treated mice. In the substantia nigra, intense immunoreactivity of nNOS-positive cells increased 5hr after MPTP treatment. Thereafter, the immunoreactivity of nNOS-positive cells decreased gradually from 1 day up to 7 days after MPTP treatment. eNOS-immunopositive cells were unchanged in the striatum and substantia nigra. These results demonstrate that nNOS may play a key role in the development of MPTP neurotoxicity. Our findings also indicate that MPTP can cause the functional damage of interneurons in the substantia nigra, but not in the striatum.Received January 30, 2003; accepted May 14, 2003 Published online August 13, 2003     

Voiding postponement in children—a systematic review

Voiding postponement (VP) has been defined as a habitual postponement of micturition using holding maneuvers. VP can represent both a symptom, as well as a condition. As divergent definitions are used internationally, the aim was to review the current state of knowledge on VP and provide recommendations for assessment, diagnosis and treatment. A Scopus and a Pubmed search was conducted, entering the terms ‘voiding postponement’ without any restrictions or specifications. Other publications relevant to the topic were added. VP can represent a symptom in healthy children. As a condition, VP in combination with nocturnal enuresis (NE) is a subtype of non-monosymptomatic NE. Most studies have focused on daytime urinary incontinence (DUI) with VP, or more aptly termed voiding postponement incontinence (VPI). It is a behaviorally defined syndrome, i.e., by the habitual deferral of micturition and DUI. VPI is associated with a low micturition frequency, urgency and behavioral problems. The most common comorbid disorder is oppositional defiant disorder (ODD). VP as a symptom and VPI as a condition should be differentiated. VPI is a common disorder with many associated problems and disorders. Urotherapy and timed voiding are the main treatment approaches. Due to the high rate of comorbid ODD, other forms of treatment, especially cognitive behavioral therapy, are often needed.     

Brain structural changes and their correlation with vascular disease in type 2 diabetes mellitus patients： a voxel-based morphometric study

Voxel-based morphometry has been used in the study of alterations in brain structure in type 1 diabetes mellitus patients. These changes are associated with clinical indices. The age at onset, pathogenesis, and treatment of type 1 diabetes mellitus are different from those for type 2 diabetes mellitus. Thus, type 1 and type 2 diabetes mellitus may have different impacts on brain structure. Only a few studies of the alterations in brain structure in type 2 diabetes mellitus patients using voxel-based morphometry have been conducted, with inconsistent results. We detected subtle changes in the brain structure of 23 cases of type 2 diabetes mellitus, and demonstrated that there was no significant difference between the total volume of gray and white matter of the brain of type 2 diabetes mellitus patients and that in controls. Regional atrophy of gray matter mainly occurred in the right temporal and left occipital cortex, while regional atrophy of white matter involved the right temporal lobe and the right cerebellar hemisphere. The ankle-brachial index in patients with type 2 diabetes mellitus strongly correlated with the volume of brain regions in the default mode network. The ankle-brachial index, followed by the level of glycosylated hemoglobin, most strongly correlated with the volume of gray matter in the right temporal lobe. These data suggest that voxel-based morphometry could detect small structural changes in patients with type 2 diabetes mellitus. Early macrovascular atherosclerosis may play a crucial role in subtle brain atro- phy in type 2 diabetes mellitus patients, with chronic hyperglycemia playing a lesser role.     

Spinal tumors in neurofibromatosis-2: Management considerations – a review

Neurofibromatosis Type 2 (NF-2) is a distinct clinical entity, characterized by multiple intracranial and spinal tumors. While bilateral vestibular schwannomas are the pathological hallmark of the disease, significant morbidity in NF-2 is attributable to the presence of both intramedullary and extramedullary spinal tumors. With the advent of MRI as a screening modality, multiple, extensive spinal tumors in the NF-2 population are often seen, which may be clinically quiescent at the time of initial diagnosis. All NF-2 patients should have routine screening with full spinal MRI at the time of diagnosis, regardless of symptoms. Early surgical intervention is indicated in cases where a neurological deficit is attributable to a focal expanding spinal lesion. In asymptomatic patients, the decision to operate is tailored to the individual patient, with the ultimate goal of preserving function. In these cases, surgery should be considered where there is evidence of progressive tumor growth, with attendant risk to the patient of functional deterioration.     

Is type 2 diabetes related to leukoaraiosis? an updated review

A significantly increased interest has been dedicated to the study of the effects of diabetes mellitus (DM) on the brain. DM is associated with an increased risk of stroke and cognitive decline. In patients with DM, neuroimaging discloses with high‐frequency structural changes, such as cerebral atrophy, infarcts and white matter lesions, also called leukoaraiosis (LA), an expression of small vessel disease. A previous review showed a relation between DM and both cerebral atrophy and lacunar infarcts, while the question about the relation between DM and LA remained unanswered. In this review, we provide an update on data on this last association. In the reviewed studies, we examined the presence of DM, other disease characteristics, such as duration and complications, and laboratory markers of the disease such as blood glycated hemoglobin (HbA1c), insulin resistance, insulin concentrations and their association with LA. About 40% of the reviewed studies reported a statistically significant association between DM and LA. Long‐standing DM and a poor glycemic control were associated with severe LA. Studies using innovative MRI techniques, such as diffusion tensor imaging (DTI), reported a significant association between microstructural white matter alterations and DM. This review highlights more firmly than previously reported the existence of a relation between DM and both presence and severity of LA. These results are possibly due to more sensitive and advanced imaging techniques recently used to study the extent of LA. However, because of the heterogeneous methodology used in the reviewed studies, a definitive conclusion cannot be drawn.     

Peripheral somatosensory stimulation and postural recovery after stroke – a systematic review

Purpose It is hypothesized that peripheral somatosensory stimulation (PSS) can promote postural recovery after stroke by increasing afferent input and postural contribution of the paretic leg. Therefore, this systematic review aims to investigate which PSS approaches are documented and investigated on effectiveness.

Methods Five databases (PubMed, Web of Science, PEDro, Cochrane Library Trials, RehabData) have been searched on clinical studies in stroke rehabilitation, investigating PSS, which is defined as a non-motor and focal stimulation to the paretic leg aiming an increase in somatosensory input.

Results Twenty studies present different PSS approaches (mainly electrical and vibration stimulation) and following results: (I) There is an immediate effect after a single session of PSS on postural stability. In contrast, (II) repetitive sessions of isolated PSS led to highly inconsistent results. Finally, (III) PSS as an adjuvant to exercises did promote long-term postural recovery.

Conclusion PSS is found to be effective immediately and on a long-term as an adjuvant therapy only in improving postural stability in a chronic stroke population. However, if PSS enhances paretic leg postural contribution remains unclear. Future research is warranted considering promising results and high prevalence of postural instability impacting daily life of stroke survivors.     

Cerebral vasculopathy in a Chinese family with neurofibromatosis type Ⅰ mutation

Neurofibromatosis type I（NF1） is a hereditary,autosomal dominant,neurocutaneous syndrome that is attributed to NF1 gene mutation.NF1 has been associated with scoliosis,macrocephaly,pseudoarthrosis,short stature,mental retardation,and malignancies.NF1-associated vasculopathy is an uncommon and easily-overlooked presentation.Examination of a Chinese family affected by NF1 combined with cerebral vessel stenosis and/ or abnormality suggested a possible relationship between NF1 and vessel stenosis.To determine which NF1 gene mutation is associated with vascular lesions,particularly cerebral vessel stenosis,we examined one rare family with combined cerebral vessel lesions or maldevelopment.Vascular lesions were detected using transcranial Doppler sonography and digital subtraction angiography in family members.Next,denaturing high-performance liquid chromatography and sequencing were used to screen for NF1 gene mutations.The results revealed a nonsense mutation,c.541C＆gt;T,in the NF1 gene.This mutation truncated the NF1 protein by 2659 aminoacid residues at the C-terminus and co-segregated with all of the patients,but was not present in unaffected individuals in the family.Exceptionally,three novel mutations were identified in unaffected family members,but these did not affect the product of the NF1 gene.Thus the nonsense mutation,c.541C＆gt;T,located in the NF1 gene could constitute one genetic factor for cerebral vessel lesions.     

Psychiatric comorbidity in patients with pediatric bipolar disorder – A systematic review

Background

A growing body of evidence suggests that pediatric bipolar disorder (PBD) frequently co-occurs with comorbid psychiatric disorders that may impact functioning.

Objective

To review existing literature on the prevalence of psychiatric comorbidity and general functioning in patients with a primary diagnosis of PBD.

Methods

We performed a systematic literature search on the PubMed, Embase and PsycInfo databases on November 16th, 2022. We included original papers on patients ≤18 years with primary PBD and any comorbid psychiatric disorder, diagnosed according to a validated diagnostic tool. Risk of bias of the individual studies was assessed using the STROBE checklist. We calculated weighted means to assess the comorbidity prevalence. The review complied with PRISMA statement guidelines.

Results

Twenty studies with a total study population of 2722 patients with PBD were included (mean age = 12.2 years). We found an overall high prevalence of comorbidity in patients with PBD. The most common comorbidities were attention-deficit-hyperactivity disorder (ADHD) (60%) and oppositional defiant disorder (ODD) (47%). Anxiety disorders, obsessive–compulsive disorder, conduct disorder, tic disorders and substance-related disorders affected between 13.2% and 29% of patients, while one in 10 had comorbid mental retardation or autism spectrum disorder (ASD). The prevalence of comorbid disorders was lower in studies that assessed the current prevalence in patients in full or partial remission. General functioning was overall not specifically decreased in patients with comorbidity.

Conclusions

Comorbidity across a broad range of disorders was high in children diagnosed with PBD, especially regarding ADHD, ASD, behavioral and anxiety disorders including OCD. Future original studies should assess current prevalence of comorbidities in patients with PBD who are in remission to obtain more reliable estimates of psychiatric comorbidity in this patient group. The review highlights the clinical and scientific importance of comorbidity in PBD.     

Dementia training programmes for staff working in general hospital settings – a systematic review of the literature

Objectives: Although literature describing and evaluating training programmes in hospital settings increased in recent years, there are no reviews that summarise these programmes. This review sought to address this, by collecting the current evidence on dementia training programmes directed to staff working in general hospitals.

Method: Literature from five databases were searched, based on a number of inclusion criteria. The selected studies were summarised and data was extracted and compared using narrative synthesis based on a set of pre-defined categories. Methodological quality was assessed.

Results: Fourteen peer-reviewed studies were identified with the majority being pre-test post-test investigations. No randomised controlled trials were found. Methodological quality was variable with selection bias being the major limitation. There was a great variability in the development and mode of delivery although, interdisciplinary ward based, tailor-made, short sessions using experiential and active learning were the most utilised. The majority of the studies mainly evaluated learning, with few studies evaluating changes in staff behaviour/practices and patients' outcomes.

Conclusion: This review indicates that high quality studies are needed that especially evaluate staff behaviours and patient outcomes and their sustainability over time. It also highlights measures that could be used to develop and deliver training programmes in hospital settings.     

Effects of Hesel-coil deep transcranial magnetic stimulation for depression – a systematic review

Background: One third of the depressed patients are not improved by antidepressant drugs and psychological treatments, and there is a need for additional treatments. Repetitive transcranial magnetic stimulation (rTMS) is being developed towards an alternative in treatment-resistant depression. Deep transcranial stimulation (dTMS) with the Hesel-coil (H-coil) is a further development of rTMS aiming to enhance the effect by getting the magnetic pulses to penetrate deeper into the brain.

Aims: This report aims to assess the evidence-base for dTMS for depression. The report also includes an assessment of the ethical and economic aspects involved.

Methods: A systematic review of the effects of H-coil dTMS on depression was conducted and the scientific support was evaluated using GRADE (Grading of Recommendations Assessment, Development and Evaluation).

Results: Only one controlled study was identified. In the sham-controlled randomized study, 212 participants with major depression that had not responded to antidepressant medication were enrolled. A two-point superiority in Hamilton Depression Rating Scale was observed in the dTMS arm vs the sham-arm at 4 weeks, but the difference was not statistically significant. No serious adverse events were reported apart from rare cases of epileptic seizures.

Conclusions: The existing scientific support for H-coil dTMS therapy for depression is insufficient. The clinical implication is that the use of dTMS in depression should be restricted to the framework of clinical trials pending further studies. Fortunately, additional studies are underway and the evidence base should presumably improve over the next several years.     

User involvement in adolescents’ mental healthcare: a systematic review

European Child & Adolescent Psychiatry - More than one out of ten adolescents suffer from mental illness at any given time. Still, there is limited knowledge about their involvement in mental...