Delirium: diagnosis, neuropathogenesis, and treatment

Delirium affects more than 2 million patients in the United States each year. The onset of delirium often occurs after hospitalization and in many cases is due to medications or procedures performed during the hospitalization. Unfortunately, delirium remains unrecognized in the majority of patients for several reasons. This review addresses the diagnostic criteria for delirium, the neurochemistry that is believed to be causative, risk factors, measures that may be taken to reduce the onset of delirium, and treatment options.     

Human microglial models to study HIV infection and neuropathogenesis: a literature overview and comparative analyses

Journal of NeuroVirology - HIV persistence in the CNS despite antiretroviral therapy may cause neurological disorders and poses a critical challenge for HIV cure. Understanding the pathobiology of...     

Mechanisms of neuropathogenesis in HIV and HCV: similarities,differences, and unknowns

HIV and hepatitis C virus (HCV) have both been associated with cognitive impairment. Combination antiretroviral therapy (cART) has dramatically changed the nature of cognitive impairment in HIV-infected persons, while the role of direct-acting antivirals (DAA) in neurocognition of HCV-infected individuals remains unclear. Also, whether HIV and HCV interact to promote neurocognitive decline or whether they each contribute an individual effect continues to be an open question. In this work, we review the virally mediated mechanisms of HIV- and HCV-mediated neuropathogenesis, with an emphasis on the role of dual infection, and discuss observed changes with HIV viral suppression and HCV functional cure on neurocognitive impairments.     

Neurogenic hypertension: pathophysiology,diagnosis and management

Clinical Autonomic Research - Discussions about the cause and treatment of essential hypertension usually focus on mechanisms such as sodium/volume and the renin–angiotensin system. Less...     

Antemortem diagnosis and prevention of human rabies

Human rabies still continues to be a significant health problem in India and other developing countries where dogs are the major vectors of transmission. Rabies in humans can present in two clinical forms, i.e., furious and paralytic. While diagnosis of furious rabies can be made based on the typical symptoms and signs, paralytic rabies poses a diagnostic dilemma to the neurologists who may encounter these cases in their practice. Although there are certain clinical features that distinguish this disease from other forms of Guillain-Barre syndromes, confirmation of diagnosis may require laboratory assistance. Conventional techniques such as antigen detection, antibody assays and virus isolation have limited success. The recently introduced molecular techniques show more promise in confirming the cases of paralytic rabies. There has not been much success in the treatment of confirmed rabies cases and recovery from rabies is extremely rare. Therefore, preventive measures of this dreaded disease after an exposure become extremely important. The present article reviews the current status of human rabies with regard to antemortem diagnosis, disease management and post-exposure prophylaxis.     

Subarachnoid hemorrhage: epidemiology, diagnosis, management, and outcome

A population-based study of primary subarachnoid hemorrhage in Auckland (population 829,454), New Zealand, identified 180 cases in a two-year period. This represented an age adjusted incidence rate of 10.5 and 18.3 per 100,000 for men and women respectively. Sixty-eight percent of all cases had a proven intracranial aneurysm or arteriovenous malformation, 15% had negative angiographic findings and in the remaining 17%, the presence or absence of a localized lesion was unknown since neither angiography nor autopsy were performed. Twenty-six patients (15%) died before hospitalization and a further 36 patients (20%) died within 48 hours of onset. Only 94 patients (53% of all patients registered) were fit enough to undergo angiography. A surgical operation was carried out on 60 of the 68 patients in whom an aneurysm was confirmed at angiography. The overall case fatality rate was 36% within the first 48 hours, 43% in the first week and 57% at both six months and one year. The high early case fatality rates are similar to those found in previous population-based studies, suggesting that despite the major advances to individual patients from technological advances, the potential contribution of hospital management to the reduction of subarachnoid haemorrhage mortality rates is likely to be limited.     

Murine coronavirus neuropathogenesis: determinants of virulence

Murine coronavirus, mouse hepatitis virus (MHV), causes various diseases depending on the strain and route of inoculation. Both the JHM and A59 strains, when inoculated intracranially or intranasally, are neurovirulent. Comparison of the highly virulent JHM isolate, JHM.SD, with less virulent JHM isolates and with A59 has been used to determine the mechanisms and genes responsible for high neuropathogenicity of MHV. The focus of this review is on the contributions of viral spread, replication, and innate and adaptive immunity to MHV neuropathogenesis. JHM.SD spreads more quickly among neurons than less neurovirulent MHVs, and is able to spread in the absence of the canonical MHV receptor, CEACAM1a. The observation that JHM.SD infects more cells and expresses more antigen, but produces less infectious virus per cell than A59, implies that efficient replication is not always a correlate of high neurovirulence. This is likely due to the unstable nature of the JHM.SD spike protein (S). JHM.SD induces a generally protective innate immune response; however, the strong neutrophil response may be more pathogenic than protective. In addition, JHM.SD induces only a minimal T-cell response, whereas the strong T-cell response and the concomitant interferon-γ (IFN-γ) induced by the less neurovirulent A59 is protective. Differences in the S and nucleocapsid (N) proteins between A59 and JHM.SD contribute to JHM.SD neuropathogenicity. The hemmagglutinin-esterase (HE) protein may enhance neuropathogenicity of some MHV isolates, but is unlikely a major contributor to the high neuroviruence of JHM.SD. Further data suggest that neither the internal (I) protein nor nonstructural proteins ns4, and ns2 are significant contributors to neurovirulence.     

Genetics and dementia: Risk factors,diagnosis, and management

New developments in molecular genetics have improved our understanding on a number of neurodegenerative dementias considerably, especially Alzheimer’s disease and frontotemporal dementia. However, this explosion of information can be overwhelming to clinicians, making it difficult to integrate into regular clinical practice. In this article, we briefly reviewed our current understanding regarding causative genetic mutations and genetic risk factors on the major forms of dementia, which provided the background information for discussion in the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. The principles of genetic counselling were applied. Guidelines and recommendations on the application of genetics in the assessment, diagnosis, and management of patients and families with dementia were summarized.     

Dystonia: diagnosis and management

Clinical practice in dystonia has greatly evolved in recent years; a synthetic review on patient management is provided here. Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures or both. A recent classification has innovated clinical practice and serves as guidance for clinical assessment: Axis I describes clinical features, whereas Axis II indicates etiology. Dystonia presents with different syndromic aggregations with varied somatic involvement and some common features. There are five recognizable physical signs of dystonia: two main signs (dystonic postures and movements) and three additional signs (gestes antagonistes or tricks, mirror dystonia and overflow dystonia). There is still no validation of diagnostic criteria for the different dystonia syndromes, and many cases with mild phenomenology remain undiagnosed. Patients with dystonia also present non‐motor features that are variably combined with the movement disorder. The features of the most common inherited and acquired dystonia syndromes are reviewed here. There is clear evidence of genetic–environmental interaction in the determinism of dystonia. The diagnostic process is guided by clinical examination and based on specific laboratory examinations. Symptomatic treatments are available for dystonia: botulinum neurotoxin injections are the primary choice for most focal dystonia syndromes; deep brain stimulation is useful in some generalized and non‐generalized syndromes. Additional treatment strategies are currently being assessed.     

Human rabies: a disease of complex neuropathogenetic mechanisms and diagnostic challenges

Rabies is inevitably fatal and presents a horrifying clinical picture. Human rabies can manifest in either encephalitic (furious) or paralytic (dumb) forms. The brainstem is preferentially involved in both clinical forms, though there are no clinical signs of brainstem dysfunction. Differences in tropism at the inoculation site or the CNS, in the route of spread, or in the triggering of immune cascades in the brainstem may account for clinical variation. Rabies still poses diagnostic problems, particularly the paralytic form, which closely resembles Guillain-Barré syndrome, or when a patient is comatose and cardinal signs may be lacking. Molecular methods allow reliable detection of rabies-virus RNA in biological fluids or tissue before death. Deviations from the recommendations on prophylaxis of the World Health Organization lead to unnecessary loss of life. To date, attempts to treat human rabies have been unsuccessful.     

Frontotemporal dementia: Its definition,differential diagnosis,and management

Background: Frontotemporal dementia (FTD) is defined as primary neurodegeneration of the anterior temporal and/or frontal lobes resulting in a group of associated conditions marked by changes in cognition, language, personality, and social functioning. FTD was previously thought to be a rare disease. However, researchers report that FTD is the third most common form of dementia. Because adults with FTD have deficits in language, cognition, and behaviour, familiarity with FTD subtypes, associated deficits, and currently available management strategies is warranted.

Aims: The aims of this tutorial are (a) to define frontotemporal dementia including behavioural and language characteristics of the three clinically distinct FTD subtypes (frontotemporal variant, nonfluent progressive aphasia, semantic dementia); (b) to identify similarities and differences between FTD and Alzheimer's dementia; and (c) to discuss management strategies for patients with FTD.

Main Contribution: Different subtypes and presentations of FTD as well as the neurological, behavioural, and language symptoms that have been consistently identified are reviewed. Behavioural and language symptoms of the two FTD subtypes with primary language disturbances (nonfluent progressive aphasia and semantic dementia) are also reviewed. Patients with FTD are frequently misdiagnosed as presenting with Alzheimer's dementia due to limitations in the literature describing the differing profiles of the two populations. When considering neurological changes, behavioural changes, language and communication behaviours, and disease progression, these patient populations are distinct and easily differentiated. Finally, management strategies are discussed. Although there is no cure for FTD, medical intervention can address some of the associated symptoms, and behavioural techniques may manage the client's environment and prolong communication abilities.

Conclusions: General discussion seeks to differentially diagnose FTD dementia from Alzheimer's dementia as well as to clarify the language and communication symptoms of FTD subtypes. Future research directions are suggested for developing evidence‐based direct and indirect management strategies.     

Behavioural-variant frontotemporal dementia: diagnosis, clinical staging, and management

Patients with behavioural-variant frontotemporal dementia (bvFTD) present with insidious changes in personality and interpersonal conduct that indicate progressive disintegration of the neural circuits involved in social cognition, emotion regulation, motivation, and decision making. The underlying pathological changes are heterogeneous and are characterised by various intraneuronal inclusions. Biomarkers to detect these histopathological changes in life are becoming increasingly important with the development of disease-modifying drugs. Gene mutations have been found that collectively account for around 10-20% of cases. Recently, criteria proposed for bvFTD define three levels of diagnostic certainty: possible, probable, and definite. Detailed history taking from family members to elicit behavioural features underpins the diagnostic process, with support from neuropsychological testing designed to detect impairment in decision making, emotion processing, and social cognition. Brain imaging is important for increasing the level of diagnostic certainty. A recently developed staging instrument shows much promise for monitoring patients and evaluating therapies, which at present are aimed at symptom amelioration. Carer education and support remain of paramount importance.     

Carotid-cavernous fistulas: Clinical features, management and differential diagnosis

Carotid-cavernous fistulas are abnormal communications between the carotid system and the cavernous sinus. Depending on their direct or indirect nature, they have different clinical manifestations and management. Are discussed in this paper: first the anatomy of the cavernous sinus, then clinical signs, diagnosis, management and differential diagnosis of carotid-cavernous fistulas.     

Depression in epilepsy: phenomenology, diagnosis and management.

1) Depression is a common and important accompaniment of epilepsy. 2) Depression in epilepsy is phenomenologically different from the usual forms of depression and it is essential that treating physicians assess for these varied forms as well. 3) Depression in epilepsy may be managed more effectively if the relationship to the ictus is better understood. 4) Other factors such as stressful life events, related or unrelated to epilepsy, may contribute to the depressive symptoms. 5) Antiepileptic drugs, particularly GABAergic agents such as vigabatrin, tiagabine, topiramate and phenobarbitone are depressogenic in nature. 6) The newer antidepressants, SSRIs such as sertraline, citalopram and paroxetine do not lower seizure threshold and can be safely used to treat depression in epileptic individuals. Fluoxetine may be avoided because of its longer half-life.