Computed tomography in the diagnosis of malignant brain tumours: do all patients require biopsy?

A proportion of patients with computed tomographic (CT) scan appearances of malignant brain tumour undergo conservative management, despite the absence of histological confirmation of the diagnosis. Concern that this policy risked misdiagnosing a benign tumour prompted us to examine the accuracy of CT scanning in diagnosing malignant lesions. The study was designed to determine whether within a group of 300 patients with intracerebral mass lesions of known pathology, two sub-groups existed: one with appearances so specific for malignant glioma that biopsy was unnecessary, and the other in which the appearances were characteristic of malignancy, though not specific for glioma. Three neuroradiologists independently reviewed the CT scans, together with brief clinical details. When diagnosing malignant tumours, all made errors: nine benign lesions were considered to be malignant. When diagnosing malignant glioma, one neuroradiologist made errors, but the other two adopted a more cautious approach and were accurate. The restricted a "certain" diagnosis to about one in five scans considered to show malignant tumour. Those diagnosed specifically as malignant glioma were intrinsic, irregular, mixed density lesions, exhibiting variable enhancement and infiltrating the peri-ventricular tissues, especially the corpus callosum. Using these criteria, they could correctly identify a small proportion of patients with malignant gliomas. In all other patients, biopsy remains the only means of obtaining a definitive diagnosis.     

How valid is the clinical diagnosis of Parkinson's disease in the community?

BACKGROUND: Many patients diagnosed with Parkinson's disease are later found to have an erroneous diagnosis, often only when they come to necropsy; conversely, many patients with Parkinson's disease in the community remain undiagnosed. OBJECTIVE: To assess the validity of a clinical diagnosis of parkinsonism in the general population according to strict published criteria. METHODS: As part of a population based study on the prevalence of Parkinson's disease in London, all patients were identified with a diagnosis of parkinsonism, tremor with onset over age 50 years, or who had ever received antiparkinsonian drugs. All patients who agreed to participate were diagnosed according to strict clinical diagnostic criteria, after a detailed neurological interview and examination and discussion of the findings with examination of their video recordings. Follow up information was obtained over a period of at least one year, and atypical cases were reviewed at the end of the study. RESULTS: A diagnosis of probable Parkinson's disease was confirmed in 83% of patients with this diagnosis, including three (2%) in whom atypical features were found that were insufficient to discard a diagnosis of Parkinson's disease. Two additional patients (2%) were found to have possible Parkinson's disease. However, in 15% of patients the diagnosis was unequivocally rejected. Conversely, 13 patients who had previously not been diagnosed with Parkinson's disease (19%) were found to have this disorder. CONCLUSIONS: At least 15% of patients with a diagnosis of Parkinson's disease in the population do not fulfil strict clinical criteria for the disease, and approximately 20% of patients with Parkinson's disease who have already come to medical attention have not been diagnosed as such.     

How do cell assemblies encode information in the brain?

The present review discusses why cell-assembly coding, i.e. ensemble coding by functionally connected neurons, is a tenable view of the brain's neuronal code and how it operates in the working brain. The cell-assembly coding has two major properties, i.e., partial overlapping of neurons among assemblies and connection dynamics within and among the assemblies. The former is the ability of one neuron to participate in different types of information processing. The latter is the capability for functional synaptic connections, detected by activity correlations of the neurons, to change among different types of information processing. An example of a series of experiments which detected these two major properties is then given. Several relevant points concerning the detection of the actual dynamics of cell-assembly coding are also enumerated. They include the dependence of the type of cell-assembly coding on types of information-processing in different structures of the brain, sparse coding by distributed overlapped assemblies, and coincidence detection as a role of individual neurons to bind distributed neurons into cell assemblies.     

How do antidepressants influence the BOLD signal in the developing brain?

Depression is a highly prevalent life-threatening disorder, with its first onset commonly occurring during adolescence. Adolescent depression is increasingly being treated with antidepressants, such as fluoxetine. The use of medication during this sensitive period of physiological and cognitive brain development produces neurobiological changes, some of which may outlast the course of treatment. In this review, we look at how antidepressant treatment in adolescence is likely to alter neurovascular coupling and brain energy use and how these changes, in turn, affect our ability to identify neuronal activity changes between participant groups. BOLD (blood oxygen level dependent) fMRI (functional magnetic resonance imaging), the method most commonly used to record brain activity in humans, is an indirect measure of neuronal activity. This means that between-group comparisons – adolescent versus adult, depressed versus healthy, medicated versus non-medicated – rely upon a stable relationship existing between neuronal activity and the BOLD response across these groups. We use data from animal studies to detail the ways in which fluoxetine may alter this relationship, and explore how these alterations may influence the interpretation of BOLD signal differences between groups that have been treated with fluoxetine and those that have not.     

Are executive skills primarily mediated by the prefrontal cortex in childhood? Examination of focal brain lesions in childhood

Introduction

Based on the study of adults with brain insult, traditional localizationist views have argued that executive skills are primarily mediated by prefrontal cortex. It remains unclear whether a similar pattern of localization exists in childhood.

Methods:

To investigate this hypothesis, we compared the performance of children, aged 7–16 years, with radiological evidence of brain pathology. The sample was divided according to lesion location as follows: frontal pathology (n = 38), extra-frontal pathology (n = 20), generalized pathology (n = 21) and healthy controls (n = 40). Using a multidimensional model of executive function described by Anderson (2002) and [Anderson, 1998] , [Anderson et?al., 2001c] and [Anderson et?al., 2001d] ), these groups were compared on a range of executive function domains including: attentional control, goal setting, cognitive flexibility, and information processing. Additional, non-executive measures were also administered.

Results

Contrary to adult lesion-based studies, there was little differentiation in executive processes between frontal and extra-frontal groups.

Conclusions

These results provide support for contemporary models which propose a distributed, but integrated neural network for executive skills, suggesting that the integrity of the entire brain is necessary for adequate executive functions in childhood. Further, focal lesions to any brain region during development may render children vulnerable to a range of executive deficits that would not normally be expected following similar pathology in adulthood.     

What clinical features precede the onset of bipolar disorder?

Despite a growing number of reports, there is still limited knowledge of the clinical features that precede the onset of bipolar disorder (BD). To explore this, we investigated baseline data from a prospectively evaluated longitudinal cohort of subjects aged 12–30 years to compare: first, lifetime rates of clinical features between a) subjects at increased genetic risk for developing BD (‘AR’), b) participants from families without mental illness (‘controls’), and c) those with established BD; and, second, prior clinical features that predict the later onset of affective disorders in these same three groups. This is the first study to report such comparisons between these three groups (though certainly not the first to compare AR and control samples). 118 AR participants with a parent or sibling with BD (including 102 with a BD parent), 110 controls, and 44 BD subjects were assessed using semi-structured interviews. AR subjects had significantly increased lifetime risks for depressive, anxiety and behavioural disorders compared to controls. Unlike prior reports, preceding anxiety and behavioural disorders were not found to increase risk for later onset of affective disorders in the AR sample, perhaps due to limited sample size. However, preceding behavioural disorders did predict later onset of affective disorders in the BD sample. The findings that i) AR subjects had higher rates of depressive, anxiety and behavioural disorders compared to controls, and ii) prior behavioural disorders increased the risk to later development of affective disorders in the BD group, suggest the possibility of therapeutic targeting for these disorders in those at high genetic risk for BD.     

Do unilateral lesions of the developing brain have side-specific psychiatric consequences in childhood?

This study used a large epidemiological sample of children with lateralised brain lesions to establish whether damage to the developing human brain has sidespecific psychiatric consequences. Parents and teachers completed behaviour questionnaires on 429 hemiplegic children and teenagers, with a subsample of 149 hemiplegic children also being assessed by parent and child interviews. Although childhood hemiplegia was accompanied by a high rate of psychopathology, children with right- and left-sided hemiplegias did not differ significantly on any dimensional or categorical measure of psychopathology. This absence of laterality effects, perhaps reflecting the developing brain's neuroplasticity, casts doubt on theories linking particular types of child or adult psychopathology to side-specific damage to the developing brain.     

How to use neuroimaging biomarkers in the diagnosis framework of neurodegenerative diseases?

Neuroimaging biomarkers, together with CSF biomarkers, are more and more used to support the early and differential clinical diagnosis of neurodegenerative diseases in clinical setting that have access to those techniques. Based on a consensus of multidisciplinary experts leading to a princeps publication in the Lancet Neurology [Chételat et al., Lancet Neurol 2020; 19: 951–62], we proposed a three-arm diagnosis algorithm detailing the optimal combination of biomarkers for the diagnosis of neurodegenerative diseases according to the clinical presentation. The main conclusions of this princeps article are summarized here, including a brief overview of the complementarity of the most validated neuroimaging biomarkers available, and an argued presentation of the proposed diagnosis algorithm.     

Addiction in the elderly - an underestimated diagnosis in clinical practice?

According to several studies in the USA, alcohol abuse is common among elder people, particularly among those admitted to hospital. Corresponding data for Germany are lacking as yet. In this study, the frequency of addiction problems in the elderly admitted to hospital was investigated using the data from 1990 to 1998 of the psychiatric department at the General University Hospital of Lübeck, Germany. Furthermore, the documentations of all consultations in that period were reevaluated. The psychiatric consultation service covers two general hospitals providing inpatient treatment for about 200,000 inhabitants. Diagnoses were made according to the ICD-10 criteria. In 17.7% of the males older than 64 years and in 4.2% of the elderly females admitted to the psychiatric department, alcohol dependency was diagnosed, while 5.8% of the elderly patients showed substance abuse, most often of benzodiazepine. Among the patients visited in the psychiatric consultation service, 10.8% of the elderly males and 3.2% of the elderly females were alcohol addicts and 3.9% substance abusers. The frequency of alcohol-induced neuropsychiatric complications, particularly withdrawal delirium and amnestic syndrome, increased with age. Also, benzodiazepine withdrawal delirium most frequently occurred in older patients. These results underscore that, although the prevalence rate seems to be lower than among the younger population, in the elderly population substance abuse still is a relevant medical problem, since the rate of neuropsychiatric complications increased with age.     

Can computerized cognitive tests assist in the clinical diagnosis of attention-deficit hyperactivity disorder?

A group of 34 children and adolescents suspected of having attention-deficit hyperactivity disorder were referred for a computerized evaluation that included sustained attention, working memory, planning, and set-shifting. Although only sustained attention had reasonable specificity, all tests had questionable contribution to the diagnostic evaluation.     

How do you perceive threat? It’s all in your pattern of brain activity

Brain Imaging and Behavior - Whether subtle differences in the emotional context during threat perception can be detected by multi-voxel pattern analysis (MVPA) remains a topic of debate. To...     

How useful are anti-neural IgM antibodies in the diagnosis of chronic immune-mediated neuropathies?

Antibodies against several neural antigens have been associated with different chronic immune-mediated neuropathies but their practical clinical relevance remains unclear. To determine the possible diagnostic usefulness of these antibodies we reviewed the clinical correlate of IgM antibodies to the myelin-associated glycoprotein (MAG), sulfatide, the gangliosides GM1, GM2, GD1a and GD1b in 539 consecutive patients examined for neuropathy or related diseases in our Neuropathy Clinics and tested for these antibodies in our laboratory since 1985. 302 patients (56%) had an established diagnosis of definite or possible chronic immune-mediated neuropathy while 237 had a neuropathy of non-immune-mediated origin or of unknown aetiology or a closely related disease. Antibodies to one or more antigen were more frequent (chi(2)=63.32; p<0.00001) in patients with chronic immune-mediated neuropathy (37.7%) than with other neuropathy or related diseases (7.2%) and their presence was associated in 87% of the patients with an immune-mediated neuropathy, incrementing by 31% the probability of having this form. Testing for MAG permitted to identify 24.8% of patients with an immune-mediated neuropathy, GM1 an additional 9.9%, while GM2, GD1b, GD1a and sulfatide altogether an additional 3% of the patients. Concerning clinical correlations, all 75 patients with anti-MAG IgM had neuropathy and IgM monoclonal gammopathy (PN+IgM) with a positive predictive value for this neuropathy of 100%. A similarly high predictive value for neuropathy (91.4%) was observed among 269 patients with IgM monoclonal gammopathy including 103 patients without neuropathy. Anti-sulfatide IgM, though rare, were also significantly and constantly associated with PN+IgM and permitted to identify few patients not bearing anti-MAG IgM. Anti-GM1 IgM were significantly associated with multifocal motor neuropathy (MMN) (29.2%) but where also found in a few patients with other immune or non-immune neuropathies or related diseases with a positive predictive value for MMN of 25.5%. Anti-GM2 IgM were also significantly associated with MMN and increased the sensitivity (36.2%) for MMN obtained with anti-GM1 IgM only, without affecting its specificity and positive predictive value. Anti-GD1a, GD1b, though not significantly more frequent in patients with immune-mediated neuropathy, were associated in 80 to 100% of patients with these neuropathies. In conclusion anti-neural IgM antibodies may help in identifying patients with a chronic immune-mediated neuropathy, even if only anti-MAG and anti-sulfatide IgM appear to be strictly associated with a definite clinical syndrome.     

Non-invasive measurement of vagus activity in the brainstem – a methodological progress towards earlier diagnosis of dementias?

Summary. In Alzheimer’s disease (AD), mild functional disturbances should precede gross structural damage and even more clinical symptoms, possibly by decades. Moreover, alterations in the brainstem are supposed to occur earlier as cortical affections. Based on these considerations, we developed a new method aiming at the measurement of vagal brainstem functioning by means of evoked potentials after electrical stimulation of the cutaneous representation of the vagus nerve in the external auditory channel. In the current study, a first sample of patients with Alzheimer’s disease (n = 7) and mild cognitive impairment (n = 3) were investigated (6m, 4f, range from 57 to 78 y, mean age 68.6 years). Vagus somatosensory evoked potentials (VSEP) were characterized by significantly longer latencies as compared to healthy age- and gender-matched controls (p < 0.05). Future large scale studies – also including preclinical stages of AD – have to assess the value of this non-invasive, fast and cheap method in the early diagnosis of neurodegenerative disorders.