Biopsychosocial approach to the human immunodeficiency virus epidemic. A clinician's primer

The human immunodeficiency virus (HIV) epidemic has created a multidimensional crisis that is challenging the health care system. Individuals with or without risk behaviors have anxieties about acquired immunodeficiency syndrome (AIDS) and need support and counseling. Once symptoms of HIV infection develop, crisis intervention and support need to be integrated into ongoing medical care. A biopsychosocial approach enables persons with AIDS to develop strategies for coping, to improve adherence, and to prevent transmission and suicide. Persons with AIDS are confronted with severe illnesses, neuropsychiatric disorders, discrimination, and death. Each person deserves the best medical and psychologic care available and the services of other disciplines where indicated. Caregivers, anxious about contagion, are devastated by the complexity, severity, and multiplicity of the illnesses that comprise AIDS and the lack of adequate resources to combat the epidemic. AIDS is a paradigm of a medical illness that requires a biopsychosocial approach. Psychiatric sequelae complicate the HIV epidemic, affecting both the uninfected and infected. The psychiatric manifestations of the uninfected include anxiety, phobia, factitious disorder, delusions, and Munchausen's AIDS. Psychiatric disorders associated with HIV infection include organic mental disorders, substance abuse disorder, affective disorders, adjustment disorders, anxiety disorders, and personality disorders. The consultation-liaison (C-L) psychiatrist is in a unique position to clarify and treat the psychiatric complications and to provide leadership for multidisciplinary programs. The biopsychosocial approach enables persons with HIV infection, their loved ones, and caregivers to meet the challenges of the HIV epidemic with compassion, optimism, and dignity.     

Memory decline evolves independently of disease activity in MS

BACKGROUND: The natural history of cognitive impairment in multiple sclerosis (MS) and its relationship with disease activity is not well known. In this study, we evaluate a prospective cohort of 44 MS patients who were followed every 3 months for 2 years. Cognitive evaluation was done at baseline and by the end of the study using the Brief Repeatable Battery-Neuropsychology. Clinical evaluation included assessment of new relapses and changes in disability (Extended Disability Status Scale (EDSS)) confirmed at 6 months. RESULTS: We found that verbal memory performance deteriorates after 2 years in patients with MS. These changes were observed in stable and active patients both in terms of relapses and disability progression, even at the beginning of the disease, and in patients with or without cognitive impairment at study entry. Attention and executive functions measured with the symbol digit modality test (SDMT) declined after 2 years in patients with confirmed disability progression. Furthermore, SDMT performance correlated with the EDSS change. CONCLUSIONS: Our findings indicate that verbal memory steadily declines in patients with MS from the beginning of the disease and independently of other parameters of disease activity.     

A mental health clinician's guide to death notification

The purpose of this article is to present an overview of past and present research to promote further understanding of the dynamics and process of death notification for mental health practitioners. This article includes information for interventionists to gain a better understanding of how their primary professional role and their own emotional vulnerabilities can impact the process. Additionally, the stress imposed on the interventionist, expected survivor reactions, and traumatic loss are discussed. Lastly, to help prepare mental health professionals who may be asked to assist in the process, a protocol for the systematic delivery of death notification information is suggested.     

A pharmacogenomic approach to Alzheimer's disease

Single nucleotide polymorphisms (susceptibility genetics) and genomic point mutations (mendelian genetics) can be used in Alzheimer's disease (AD) for diagnostic, predictive and therapeutic purposes. Using a matrix genetic model, including APOE, PS1 and PS2 allelic variants, we have studied the distribution of 36 different genotypes in the AD population ( N =479) and the genotype-related cognitive response to a multifactorial therapy in AD patients with mild-to-moderate dementia. The 10 most frequent AD genotypes are the following: 1) E33P112P2+ (17.75%), 2) E33P112P2− (15.55%), 3) E33P111P2+ (10.85%), 4) E34P112P2+ (9.60%), 5) E34P112P2− (7.56%), 6) E33P111P2− (7.10%), 7) E34P111P2+ (4.80%), 8) E33P122P2+ (4.38%), 9) E34P111P2− (4.18%), and 10) E34P122P2+ (3.55%). APOE-4/4-related genotypes represent less than 3% in the following order: E44P112P2+> E44P111P2+=E44P111P2−>E44P112P2+>E44P122P2+= E44P122P2−. Multifactorial therapy with CDP-choline (1000 mg/day)+piracetam (2400 mg/day)+anapsos (360 mg/day) did improve mental performance during the first 6–15 months in a genotype-specific fashion. The best responders in the APOE series were patients with APOE-3/4 genotype ( r =+0.013), while the worst responders were APOE-4/4 patients ( r =−0.93). PS1-related genotypes responded in a similar manner; and patients with a defective PS2 gene exon 5 (PS2+) always showed a poorer therapeutic response than PS2− patients. All these data suggest that the therapeutic outcome in AD exhibits a genotype-specific pattern, and that a pharmacogenomic approach to AD might be a valuable strategy for drug development and monitoring.     

Nutritional approaches to modulate oxidative stress in Alzheimer's disease

Alzheimer's disease (AD) brain is characterized by amyloid β-peptide (Aβ) deposits, neurofibrillary tangles, synapse loss, and extensive oxidative stress. Aβ-induced oxidative stress is indexed by protein oxidation, lipid peroxidation, free radical formation, DNA oxidation and neuronal cell death. Oxidative stress is combated by antioxidants. Antioxidants and nutrition have long been considered as an approach to slow down AD progression. In this review, we focus on antioxidants that have been shown to protect against Aβ-induced oxidative stress, particularly vitamin E, ferulic acid, various polyphenols, including quercetin and resveratrol, α-lipoic acid, N-acetyl-L-cysteine (NAC), curcumin, epigallocatechin gallate (EGCG), and γ-glutamylcysteine ethyl ester (GCEE). Brain-accessible antioxidants with both radical scavenging properties and ability to induce protective genes are hypothesized to be helpful in treatment for AD.     

Pulsed corticosteroid treatment in MS patients stabilizes disease activity following natalizumab withdrawal prior to switching to fingolimod

Purpose: Interruption of natalizumab (NTM) treatment in multiple sclerosis (MS) patients may be followed by disease reactivation. On the other hand, patients with positive John Cunningham virus (JCV) antibodies treated with NTM over 24 months demonstrate a higher risk for developing progressive multifocal encephalopathy (PML). No established therapeutic approach is available for treating these patients to prevent disease reactivation. Materials and methods: Of the MS patients treated with NTM at the authors’ institution, 30 were found positive for JCV abs. NTM was interrupted followed by a washout period of 6 months. During this period, 20/30 patients received monthly intravenous (i.v.) methylprednisolone (MPD) 1000 mg infusion and regular clinical assessment. On months 3 and 6, brain MRI was performed and 1000 mg MPD was administered for 5 days. Results: All patients were clinically and radiologically stable at the time of NTM break. No clinical relapse was observed during the six-month washout period for the MS patients under monthly MPD treatment, while one patient had a relapse and active lesions in the MRI on month 6. Of the other patients not receiving i.v. MPD regularly after NTM withdrawal, one showed several active lesions in brain MRI and the other had a severe relapse. Conclusions: Despite the limited size of this patients’ cohort, the results of this study support that monthly MPD treatment for 6 months may result in a clinically stable disease status, thus ensuring safe transition to another second-line therapy such as fingolimod, following NTM withdrawal.     

Association between clinical disease activity and Epstein-Barr virus reactivation in MS

OBJECTIVE: To assess the potential significance of Epstein-Barr virus (EBV) reactivation in disease activity in MS patients. METHODS: The prevalence of antibodies against herpes simplex virus type 1 (HSV-1), HSV-2, EBV, and cytomegalovirus was determined in a group of 108 MS patients and in 163 healthy control subjects. Sera were analyzed using combinations of novel assay systems employing highly purified viral and recombinant antigens. In addition, PCR for the detection of EBV DNA was performed in serial samples. RESULTS: In contrast to the control populations, antibodies against EBV were present in 100% of MS patients. Among the tested human herpesviruses, this high extent of seropositivity was only found for EBV. Primary infection was found exclusively in the control group (3.7%), whereas serologic evidence of EBV reactivation was seen in MS patients (13. 9%) as well as control subjects (17.2%). There was no temporal coincidence between EBV reactivation and disease activity in MS patients. However, in 19 patients followed monthly for 1 year, active viral replication as measured by increased immunoglobulin (Ig) M and IgA responses to EBV early antigens (p54 + p138) and positive serum DNA was seen in 72.7% of patients with exacerbations during the study period and in none of the patients with clinically stable disease. CONCLUSIONS: The results demonstrate an association between EBV reactivation and disease activity in MS patients over time, and suggest that EBV might play an indirect role in MS as an activator of the underlying disease process.     

A new approach in the assessment of motor activity in Parkinson''s disease.

Motor activity was recorded continuously with a wrist-worn activity monitor for almost six days in nine patients with different predominant manifestations of Parkinson's disease and 10 normal subjects. The indices of diurnal motor activity decreased with the progressive worsening of hypokinesia and rigidity. With this monitor and a simple diary it was possible to determine the contribution of a moderate resting tremor and choreiform dyskinesias to the motor activity level, and to monitor their variability.     

Seasonal variation in immune measurements and MRI markers of disease activity in MS

BACKGROUND: The exact mechanisms by which T cells contribute to MS progression are not known. Recently, the results of cross-sectional studies suggested seasonal variation of both interferon (IFN)-gamma production and the number of active MRI lesions in MS. OBJECTIVE: To investigate whether seasonal fluctuations of IFN-gamma and active MRI lesions could be confirmed and whether any correlations could be detected. METHODS: Data were analyzed from a group of 28 MS patients in whom detailed longitudinal monitoring of both immune function and MRI measurements had taken place. RESULTS: Significant seasonal variation was observed in T-cell activation as measured by the ability of T cells to secrete the pro-inflammatory cytokines tumor necrosis factor-alpha and IFN-gamma. Maximum values were found in samples obtained during autumn. Even though clear fluctuations were observed, no significant seasonal variation could be detected in the number of active MRI lesions. Fluctuations of in vitro IFN-gamma secretion correlated weakly with changes in active MRI lesions. CONCLUSIONS: The finding of seasonal variation of immune function in serially MRI-monitored MS patients suggests an environmental role in T-cell activation.