Risdiplam for the Use of Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is one of the leading causes of death in infants related to the degeneration of neurons. Currently, there are no curative treatment options for SMA, and many options available may not be feasible. This review presents the background, clinical studies, and indications for the use of Risdiplam in treating SMA. SMA causes a decrease in the production of survival motor neuron proteins (SMN) and current treatments target to increase the expression of SMN. Risdiplam is the first and only oral medication to be approved to treat SMA. As an SMN2 splicing modifier, it has provided stronger systemic therapies than previous intrathecal and gene replacement therapies. There have been many efforts to treat SMA with multidisciplinary approaches. These include intrathecal injections to gene replacement therapies. However, these have been faced with limitations such as reaching a good therapeutic dose in systemic tissues, route of administration, and price. Risdiplam is currently the only orally administered drug approved by the FDA for the treatment of SMA. It not only provides a good therapeutic window to systemic tissues but allows for a non-invasive approach in infants. Further investigation and comparison on the safety profile of Risdiplam due to its broader systemic effect should be considered with other available therapies.

Using an implicit memory task to estimate premorbid memory.

Clinicians are often asked to determine if significant memory loss has occurred. Clinical judgment figures prominently in making these determinations, because there is no accepted, objective method for estimating premorbid memory. Two studies were designed to explore the utility of an implicit memory task, Anagrams Solutions, for estimating premorbid memory ability. A secondary goal was to identify predictors of immediate and delayed memory measured by the Repeatable Battery for the Assessment of Neuropsychological Status using selected intellectual (IQ) and demographic variables. Participants in both studies were administered the implicit memory task, explicit memory measures, and IQ estimate. Results revealed that Anagrams Solutions was not a useful estimate of premorbid memory and that a combination of IQ and demographic variables accounted for 24-31% of the variance in measured memory performances. Findings point to the need for caution in interpreting scores on these variables as valid estimates of premorbid memory functioning.

Utility of the RBANS in detecting cognitive impairment associated with Alzheimer's disease: sensitivity, specificity, and positive and negative predictive powers.

Although initially developed as a brief dementia battery, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) has not yet demonstrated its sensitivity, specificity, and positive and negative predictive powers in detecting cognitive impairment in patients with Alzheimer's disease (AD). Therefore, the current study examined the clinical utility of the RBANS by comparing two age-, education-, and gender-matched groups: patients with AD (n=69) and comparators (n=69). Significant differences (p<0.001) were observed on the RBANS Total score, all 5 Indexes, and all 12 subtests, with patients performing worse than the comparison participants. An optimal balance between sensitivity and specificity on RBANS scores was obtained when cutoffs of one and one and a half standard deviations below the mean of the comparison sample were implemented. Areas under the Receiver Operating Characteristic curves for all RBANS Indexes were impressive though Immediate and Delayed Memory Indexes were excellent (0.96 and 0.98, respectively). Results suggest that RBANS scores yield excellent estimates of diagnostic accuracy and that the RBANS is a useful screening tool in detection of cognitive deficits associated with AD.

Early symptom predictors of chronic distress in Gulf War veterans.

Although there is evidence that specific early hyperarousal, avoidance, and emotional numbing symptoms are associated with later posttraumatic stress disorder (PTSD) symptomatology among veterans, little is known about predictors of later non-PTSD-related psychological symptoms. One and 2 years after serving in the Gulf War, 348 military reservists were assessed for severity of war zone stress, PTSD, psychological distress, and stress-mediated physical complaints. Overall PTSD symptomatology and emotional numbing and hyperarousal symptom clusters increased over time, whereas re-experiencing and avoidance symptoms showed no change. Emotional numbing and hyperarousal symptoms at 1 year predicted generalized distress, depression, anxiety, hostility, and somatic symptoms at 2 years, whereas re-experiencing and avoidance symptoms did not. Findings highlight the importance of targeting early emotional numbing and hyperarousal symptom clusters to reduce longer-term psychological distress.

Olfactory functioning in Gulf War-era veterans: relationships to war-zone duty, self-reported hazards exposures, and psychological distress.

To explore possible neurotoxic sequelae of Gulf War (GW) participation, olfactory identification performance, neurocognitive functioning, health perceptions, and emotional distress were assessed in 72 veterans deployed to the GW and 33 military personnel activated during the GW but not deployed to the war zone. Findings revealed that war-zone-exposed veterans reported more concerns about health, cognitive functioning, and depression than did their counterparts who did not see war-zone duty. There was no evidence that performances on olfactory or neurocognitive measures were related to war-zone duty or to self-reported exposure to GW toxicants. However, symptoms of emotional distress were positively correlated with self-report of health and cognitive complaints. Results do not provide support for the hypothesis that objectively-measured sensory (i.e., olfactory) or cognitive deficits are related to war-zone participation but do underscore the increasingly demonstrated association between self-reported health concerns and symptoms of emotional distress.

Attention, learning, and memory performances and intellectual resources in Vietnam veterans: PTSD and no disorder comparisons.

Attention, learning, memory, and estimated intellectual potential were examined in 26 Vietnam veterans diagnosed with posttraumatic stress disorder (PTSD) and in 21 Vietnam veterans without mental disorders. Results revealed PTSD-associated cognitive deficits on tasks of sustained attention, working memory, initial learning, and estimated premorbid intelligence but not on measures of focus of attention, shift of attention, or memory savings. Cognitive task performances adjusted for estimated native intelligence remained negatively correlated with PTSD severity. An intellectual measure adjusted for cognitive task performances was negatively correlated with PTSD severity, even after the authors statistically controlled the level of combat exposure. Results suggested that although intellectual resources may constitute a vulnerability-protective factor for PTSD development, PTSD was associated with cognitive impairment independent of intellectual functioning.

Anxiety and pain response changes across treatment: sensory decision analysis.

Relationships between anxiety and pain perception were investigated by comparing pre- and post-pain reactions of highly anxious detoxified substance abusers categorized on the basis of anxiety level changes over treatment. Sensory decision theory methodology was applied to measure discriminative and decisional aspects of pain response. Men exhibiting significant pre-post-anxiety state decreases showed greater discriminability index increases and greater response bias index decreases at post-test, compared to their counterparts exhibiting minimal changes in severe anxiety levels across treatment. Findings have relevance for understanding pain perception and interventions in clinical samples.