Brain imaging technologies: how, what, when and why?

OBJECTIVE: Innovations in physics and computing technology over the past two decades have provided a powerful means of exploring the overall structure and function of the brain using a range of computerised brain imaging technologies (BITs). These technologies offer the means to elucidate the patterns of pathophysiology underlying mental illness. The aim of this paper is to explore the current status and some of the future directions in the application of BITs to psychiatry. METHOD: Brain imaging technologies provide unambiguous measures of brain structure (computerised tomography and magnetic resonance imaging [MRI]) and also index complementary measures of when (electroencephalography, event related potentials, magnetoencephalography) and where (functional MRI, single photon emission computed tomography, positron emission tomography) aspects of brain activity occur. RESULTS: The structural technologies are primarily used to exclude a biological cause in cases of a suspected psychiatric disorder. The functional technologies show considerable potential to delineate subgroups of patients (that may have different treatment outcomes), and evaluate objectively the effects of treatment on the brain as a system. What is seldom emphasised in the literature are the numerous inconsistencies, the lack of specificity of findings and the simplistic interpretation of much of the data. CONCLUSION: Brain imaging technologies show considerable utility, but we are barely scratching the surface of this potential. Simplistic over-interpretation of results can be minimised by: replication of BIT findings, judicious combination of complementary methodologies, use of appropriate activation tasks, analysis with respect to large normative databases, control for performance, examining the data'beyond averaging', delineating clinical subtypes, exploring the severity of symptoms, specificity of findings and effects of treatment in the same patients. The technological innovation of BITs still far outstrips the sophistication of their use; it is essential that the meaning and mechanisms underlying BIT measures are always evaluated with respect to prevailing models of brain function across disciplines.     

Vascular diagnosis and acute stroke: what, when and why not?

Even within the 3-hour time window, the less the delay to thrombolysis, the more likely it is to be effective. Delays caused by unnecessary examinations based on physicians' uncertainty about the relevance of vascular diagnostics must be overcome if acute therapy is to be administered efficiently. Only defined information concerning inclusion and exclusion criteria, a CT or preferably an MRI of the brain and limited additional data should be achieved prior to treatment and as quickly as possible, preferably within 1 h. All other information is to be gathered after the start of treatment, to assess the possible etiology of stroke, to classify the prognosis, and to recognize the possible need for early intervention such as in carotid stenosis. A primary diagnostic approach with MRI-guided treatment decision should be limited to cases with uncertain or 3- to 9-hour time window to improve selection of patients potentially at benefit from specific treatment and stroke unit/ICU care.     

Invasive EEG monitoring in children: when, where, and what?

With rapid advances in noninvasive technology, the need for chronic intracranial monitoring to define the epileptogenic region has diminished significantly. Its role in presurgical evaluation has come under scrutiny particularly in adults with lesional epilepsy. With the shift in surgical candidacy toward the younger age groups, however, invasive monitoring has regained its utility especially in children with normal imaging studies and cortical dysplasia. This review critically evaluates its continuing role, attempting to assess cost-benefit under specific clinical scenarios and proposes how the findings can be incorporated into the challenging task of surgical planning in intractable childhood epilepsy.     

Treating early psychosis: who,what, and when?

Early intervention and prevention in schizophrenia is just over 10 years old. The assumption guiding this field is that intervention is likely to be most effective if it begins before psychosis sets in, ie, during the prodromal phase. Although a substantial number of prodromal treatment programs have been initiated around the world, three early programs have generated most of the intervention findings to date: Personal Assessment and Crisis Evaluation (PACE) in Australia, and the Prevention through Risk Identification, Management, and Education (PRIME) and Recognition and Prevention (RAP) programs in the USA. The data suggest that early intervention leads to a reduction in prodromal symptoms and clinical distress. However, prevention of psychosis remains an unresolved question. Other issues include defining who should be treated, with what, and when. In addition, treatment targets associated with functional disability, such as early prodromal negative symptoms and risk factors, continue to emerge. Newly identified targets, in turn, suggest the need for a variety of novel interventions and treatment strategies.     

Schizophrenias and epilepsies: why? when? how?

Detailed studies of the association between the epilepsies and the schizophrenias extend over 40 years. Recent studies are abundant and make fertile use of new technologies. However, the pathological changes described in schizophrenias are quite varied. Studies fail to recognize that "epilepsies" and "schizophrenias" have varied in definition over time, and have always been weak categories with which to do science. Now that it is possible to measure deficits in brain structure, it would be better to see what behavioral problems are associated with specific cerebral pathology. It would be wise to be very precise in describing the behaviors and the nature and timing of their emergence rather than using terms such as psychoses. Schizophrenias have neurological, neuropsychological, and behavioral antecedents in childhood. Those associated with later epilepsies show biases, persistent in many studies over a number of years, toward relative excess of females, left temporal lobe structural deficits, and non-right-handedness. Schizophrenia should now be a predictable eventuality in certain people with epilepsies, an important factor in medical and surgical treatment.     

Intraoperative neurophysiological monitoring in pediatric neurosurgery: why, when, how?

INTRODUCTION: This review is primarily based on peer-reviewed scientific publications and on the authors' experience in the field of intraoperative neurophysiology. The purpose is a critical analysis of the role of intraoperative neurophysiological monitoring (INM) during various neurosurgical procedures, emphasizing the aspects that mainly concern the pediatric population. Original papers related to the field of intraoperative neurophysiology were collected using medline. INM consists in monitoring (continuous "on-line" assessment of the functional integrity of neural pathways) and mapping (functional identification and preservation of anatomically ambiguous nervous tissue) techniques. We attempted to delineate indications for intraoperative neurophysiological techniques according to their feasibility and reliability (specificity and sensitivity). DISCUSSION AND CONCLUSIONS: In compiling this review, controversies about indications, methodologies and the usefulness of some INM techniques have surfaced. These discrepancies are often due to lack of familiarity with new techniques in groups from around the globe. Accordingly, internationally accepted guidelines for INM are still far from being established. Nevertheless, the studies reviewed provide sufficient evidence to enable us to make the following recommendations. (1) INM is mandatory whenever neurological complications are expected on the basis of a known pathophysiological mechanism. INM becomes optional when its role is limited to predicting postoperative outcome or it is used for purely research purposes. (2) INM should always be performed when any of the following are involved: supratentorial lesions in the central region and language-related cortex; brain stem tumors; intramedullary spinal cord tumors; conus-cauda equina tumors; rhizotomy for relief of spasticity; spina bifida with tethered cord. (3) Monitoring of motor evoked potentials (MEPs) is now a feasible and reliable technique that can be used under general anesthesia. MEP monitoring is the most appropriate technique to assess the functional integrity of descending motor pathways in the brain, the brain stem and, especially, the spinal cord. (4) Somatosensory evoked potential (SEP) monitoring is of value in assessment of the functional integrity of sensory pathways leading from the peripheral nerve, through the dorsal column and to the sensory cortex. SEPs cannot provide reliable information on the functional integrity of the motor system (for which MEPs should be used). (5) Monitoring of brain stem auditory evoked potentials remains a standard technique during surgery in the brain stem, the cerebellopontine angle, and the posterior fossa. (6) Mapping techniques (such as the phase reversal and the direct cortical/subcortical stimulation techniques) are invaluable and strongly recommended for brain surgery in eloquent cortex or along subcortical motor pathways. (7) Mapping of the motor nuclei of the VIIth, IXth-Xth and XIIth cranial nerves on the floor of the fourth ventricle is of great value in identification of "safe entry zones" into the brain stem. Techniques for mapping cranial nerves in the cerebellopontine angle and cauda equina have also been standardized. Other techniques, although safe and feasible, still lack a strong validation in terms of prognostic value and correlation with the postoperative neurological outcome. These techniques include monitoring of the bulbocavernosus reflex, monitoring of the corticobulbar tracts, and mapping of the dorsal columns. These techniques, however, are expected to open up new perspectives in the near future.     

Foot drop: where, why and what to do?

Foot drop is a common and distressing problem that can lead to falls and injury. Although the most frequent cause is a (common) peroneal neuropathy at the neck of the fibula, other causes include anterior horn cell disease, lumbar plexopathies, L5 radiculopathy and partial sciatic neuropathy. And even when the nerve lesion is clearly at the fibular neck there are a variety of causes that may not be immediately obvious; habitual leg crossing may well be the most frequent cause and most patients improve when they stop this habit. A meticulous neurological evaluation goes a long way to ascertain the site of the lesion. Nerve conduction and electromyographic studies are useful adjuncts in localising the site of injury, establishing the degree of damage and predicting the degree of recovery. Imaging is important in establishing the cause of foot drop be it at the level of the spine, along the course of the sciatic nerve or in the popliteal fossa; ultrasonography, CT and MR imaging are all useful. For patients with a severe foot drop of any cause, an ankle foot orthosis is a helpful device that enables them to walk better and more safely.     

The role of dopamine in conditioning and latent inhibition: what, when, where and how?

It is well established that dopamine is released in the nucleus accumbens (NAC) in animals in rewarding or reinforcing situations, and widely believed that this release is the substrate of, or at least closely related to, the experience of reward. The demonstration of conditioned release of dopamine by stimuli conditioned to primary rewards has reinforced this view. However, a number of observations do not sit comfortably with this interpretation, most notably that dopamine is released equally effectively in NAC by aversive stimuli, and stimuli conditioned to them. Furthermore, additional release of dopamine is seen during conditioning, even if motivational stimuli of either type are not involved. It is suggested here that one important action of NAC dopamine release is to restore the salience of potential conditioned stimuli, when this has been reduced by prior un-reinforced experience. The paradigm of latent inhibition (LI) demonstrates a behavioural effect of this type, and extensive studies on the role of dopamine in LI have been undertaken by us and others. Those studies are reviewed here, together with some previously unpublished data, to demonstrate that (1) amphetamine disruption of LI is indeed a function of calcium-dependant dopamine release in the NAC at the time of conditioning; (2) other drugs acting on LI via changes in dopamine transmission act at the same locus; (3) the disruptive effect of indirect dopamine agonists on LI can be prevented by either D-1 selective receptor antagonists, or D-2 selective receptor antagonists. It is concluded that dopamine release in these very varied behavioural contexts (reward, punishment, conditioning, modulation of salience) must be differentiated in some way, and that this should be investigated. An alternative explanation, if they are not differentiated, would be that the release in fact does have the same functional significance in each case. We suggest that this common significance might be the broadening of attention to take in potentially conditionable stimuli, which have previously been devalued.     

Effectiveness, transportability, and dissemination of interventions: what matters when?

The authors identify and define key aspects of the progression from research on the efficacy of a new intervention to its dissemination. They highlight the role of transportability questions that arise in that progression and illustrate key conceptual and design features that differentiate efficacy, effectiveness, and dissemination research. An ongoing study of the transportability of multisystemic therapy is used to illustrate independent and interdependent aspects of effectiveness, transportability, and dissemination studies. Variables relevant to the progression from treatment efficacy to dissemination include features of the intervention itself as well as variables pertaining to the practitioner, client, model of service delivery, organization, and service system. The authors provide examples of how some of these variables are relevant to the transportability of different types of interventions. They also discuss sample research questions, study designs, and challenges to be anticipated in the arena of transportability research.     

Parkinson’s disease DBS: what, when, who and why? The time has come to tailor DBS targets

Deep brain stimulation (DBS) has recently been proven to be an effective therapy for medication refractory symptoms of Parkinson's disease. As the evidence base continues to evolve, many important issues have surfaced, including: what operation should be performed (brain target[s],unilateral vs bilateral, simultaneous vs staged); when to operate (how early is too early to intervene?), who should be operated on (disease duration, age, symptom profiles and the use of the interdisciplinary screening team); and finally, why to operate (the rationale of surgery vs medication/apomorphine pumps/duodopa pumps/stem cell trials/gene therapy trials). We will address each of these critical issues, as well make the argument that a tailored approach to DBS and DBS targeting will best serve each potential candidate. We will review the multiple peer reviewed studies and we will emphasize the recently available data from randomized DBS studies.We will argue that moving away from a single DBS target (e.g., subthalamic nucleus DBS) and a single approach to DBS methodology (e.g., bilateral simultaneous operations) is a reasonable next step for the Parkinson's disease community. Following careful interdisciplinary DBS screening, a physician-patient discussion has the potential to establish a patient-centered and symptom-specific outcome for each potential DBS candidate. The interdisciplinary DBS team can function together to formulate and to consider an optimal and tailored approach. A tailored approach will allow for the consideration of the complex and numerous variables that may contribute to a positive or negative overall DBS outcome. We will review and provide expert commentary on a potential interdisciplinary approach to selecting unilateral or alternatively bilateral subthalamic nucleus or globus pallidus internus DBS. Our approach is aimed to maximize benefit(s) and minimize risk(s) in order to best tailor therapy for an individual patient.     

Management of hydrocephalus in posterior fossa tumors: how,what, when?

Object The aim of this work is to analyze the current management of hydrocephalus associated with posterior fossa (PF) tumors.Methods The personal perspectives of experienced pediatric neurosurgeons were presented at a virtual round table.Discussion Preoperative hydrocephalus has been reported in about 80% of patients with PF tumors and postoperative treatment is required for persistent or progressive hydrocephalus in about 25–30% of the cases. Preoperative management includes external ventricular drainage (EVD), endoscopic third ventriculostomy (ETV), shunt insertion, and no treatment at all, while ETV and ventriculo-peritoneal (V-P) shunt are recommended as treatment after PF craniotomy.Conclusion There is no consensus on the way hydrocephalus should be managed before, during, and after PF surgery. While awaiting prospective multicenter trials of various management schemes the perioperative management of hydrocephalus in the context of posterior fossa tumors should be considered as options.