Cognitively impaired patients with HIV have similar beta-amyloid1-42 (Ab42) measurements in CSF to those of patients with mild dementia of the Alzheimer type, according to a study in the December 8, 2009, Neurology. Researchers obtained CSF specimens from cognitively normal subjects from the general population, as well as HIV-positive subjects with either normal or impaired cognition, and subjects presumed HIV negative with mild dementia of the Alzheimer type. “CSF Ab42 measured in 49 HIV-associated neurologic disorders subjects had a median level of 501 pg/mL, which was lower than that of 50 controls of similar age who had a median of 686 pg/mL, or 21 HIV-positive subjects without cognitive impairment who had a median of 716 pg/ml,” the researchers stated. “Normal or slightly depressed CSF tau and p-tau181 measurements distinguish these patients with HIV-associated neurologic disorders from patients with dementia of the Alzheimer type.”

Clinical, cognitive, and CSF markers consistent with Alzheimer’s disease may precede detection of cerebral beta-amyloid with amyloid imaging agents such as Pittsburgh Compound-B (PiB), which primarily label fibrillar beta-amyloid plaques, as reported in the December 2009 Archives of Neurology. Decline in measures of episodic memory, and to a lesser degree, working memory, began at about age 88 in the participant. “PiB-PET amyloid imaging was negative at age 88.5 years, but at age 89.5 years there was reduced Ab42 and elevated levels of tau in the CSF,” the investigators stated. The patient was diagnosed with mild dementia of the Alzheimer type around age 90. “Postmortem biochemical analysis of the cerebral tissue confirmed that PiB-PET-binding was below the level needed for in vivo detection.”

Patients with subjective cognitive impairment (SCI) have an increased risk for further decline during a seven-year period, according to a study in the January Alzheimer’s and Dementia. A consecutive series of healthy subjects (age 40+, 60% female) presenting with either no cognitive impairment (NCI) or SCI were followed up for a mean period of 6.8 years. “Controlling for baseline demographic variables and follow-up time, Weibull proportional hazards model revealed increased decline in SCI subjects (hazard ratio, 4.5), whereas the accelerated failure time model analysis with an underlying Weibull survival function showed that SCI subjects declined more rapidly, at 60% the rate of NCI subjects,” researchers stated. “Furthermore, mean time to decline was 3.5 years longer for NCI than for SCI subjects.”

Long-term, high-frequency electromagnetic field (EMF) exposure directly related to cell phone use (918 MHz; 0.25 w/kg) provides cognitive benefits, according to a study in the January Journal of Alzheimer’s Disease. “In Alzheimer’s disease mice, long-term EMF exposure reduced brain beta-amyloid deposition through beta-amyloid anti-aggregation actions and increased brain temperature during exposure periods,” the authors stated. They proposed several mechanisms of EMF action, including increased beta-amyloid clearance from the brains of Alzheimer’s disease mice, increased neuronal activity, and increased cerebral blood flow. “Although caution should be taken in extrapolating these mouse studies to humans, we conclude that EMF exposure may represent a noninvasive, nonpharmacologic therapeutic [benefit] against Alzheimer’s disease and an effective memory-enhancing approach in general.”

Patients with autism may experience an M100 latency delay, indicative of disruption of encoding simple sensory information, according to a study in the January 8 online Autism Research. Investigators obtained whole-cortex magnetoencephalography from 17 typically developing children and 25 children with autism spectrum disorder (ASD). Tones with frequencies of 200, 300, 500, and 1,000 Hz were presented, and left and right superior temporal gyrus activity were examined. “Examining the right hemisphere 500 Hz condition (where the largest latency differences were observed), a sensitivity of 75%, specificity of 81%, and a positive predictive value of 86% were obtained at a threshold of 116 msec,” the researchers stated. “Given similar findings in language-impaired and nonlanguage-impaired ASD subjects, a right-hemisphere M100 latency delay appears to be an electrophysiologic endophenotype for autism.”

Ephrin stimulation in patients with autism inactivates the mTOR pathway by enhancing TSC2 activity, according to a report in the January 10 online Nature Neuroscience. “We found that TSC2 haploinsufficiency in mice caused aberrant retinogeniculate projections that suggest defects in EphA receptor-dependent axon guidance,” researchers stated. “We also found that EphA receptor activation by ephrin-A ligands in neurons led to inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) activity and decreased inhibition of TSC2 by ERK1/2.” In addition, TSC2 deficiency and hyperactive Rheb activated mTOR and inhibited ephrin-induced growth cone collapse. “Our results indicate that TSC2-Rheb-mTOR signaling cooperates with the ephrin-Eph receptor system to control axon guidance in the visual system,” the investigators concluded.

Antiepileptic drugs (AEDs) do not increase the risk of suicide attempts in patients with bipolar disorder relative to those not treated with AEDs or lithium, according to a study published in the December 2009 Archives of General Psychiatry. In addition, AED use reduces the rates of suicide attempts both relative to patients not receiving psychotropic medication and relative to their pretreatment levels. Researchers conducted a pharmacoepidemiologic study in which rates of suicide attempts were compared before and after treatment, and against a medication-free control group. “Overall, there was no significant difference in suicide attempt rates for patients treated with an AED (13 per 1,000 person-years) versus patients not treated with an AED or lithium (13 per 1,000 person-years),” the investigators stated. “In AED-treated subjects, the rate of suicide attempts was significantly higher before treatment (72 per 1,000 person-years) than after (13 per 1,000 person-years).”

The deletion of suppressor of cytokine signaling 3 (SOCS3) in adult retinal ganglion cells promotes axon regeneration via a gp130-dependent pathway, according to a report in the December 10, 2009, Neuron. After analyzing axon regeneration in various mutant mouse lines, investigators found that deletion of SOCS3 aided robust regeneration of injured optic nerve axons. In addition, a transient upregulation of ciliary neurotrophic factor (CNTF) was seen within the retina following nerve injury. Axon regeneration from SOCS3-deleted RCGs was further enhanced by intravitreal application of CNTF. “Together, our results suggest that comprised responsiveness to injury-induced growth factors in mature neurons contributes significantly to regeneration failure,” the researchers stated.

Multiple sclerosis spasticity symptoms may be controlled by a combination of Delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD) extracts, according to a report in the December 4, 2009, online BMC Neurology. Investigators systematically reviewed six studies for treatment dosage and duration, objective and subjective measures of spasticity, and reports of adverse events. “Although there was variation in the outcome measures reported in these studies, a trend of reduced spasticity in treated patients was noted,” the investigators stated. “Although some objective measures of spasticity noted improvement trends, there were no changes found to be significant in posttreatment assessments,” stated the researchers. “However, subjective assessment of symptom relief did often show significant improvement posttreatment.”

The European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria allow for a high identification of patients with chronic inflammatory demyelinating polyneuropathy, according to a report in the December 2009 Journal of Neurology, Neurosurgery, and Psychiatry. EFNS/PNS criteria were compared with newly published criteria by Koski et al. Results were compared with the investigators’ criteria, and those of the American Academy of Neurology (AAN). Koski et al’s criteria had a 63% sensitivity and 99.3% specificity. EFNS/PNS criteria showed an 81.3% sensitivity and 96.2% specificity. The investigators’ criteria had a 79.5% sensitivity and a 96.9% specificity. AAN criteria were poorly sensitive (45.7%) but were 100% specific. “In our patient populations, the EFNS/PNS criteria were the most sensitive and allowed identification of a highly significant greater number of patients than Koski et al’s criteria,” the researchers concluded.

People born in the US stroke belt have an elevated stroke mortality, per a study in the December 1, 2009, Neurology. Those who also live in a stroke belt state (North Carolina, South Carolina, Georgia, Tennessee, Arkansas, Mississippi, or Alabama) during adulthood have an increased risk. Researchers observed stroke mortality rates for US born black and white people (ages 30 to 80) for 1980, 1990, and 2000 for strata defined by birth state and state of adult residence. “Compared to those living outside the stroke belt at birth and adulthood, odds ratios for stroke belt residence at birth and adulthood for black subjects were 1.55 in 1980, 1.47 in 1990, and 1.34 in 2000,” the investigators stated. “Comparable odds ratios for white subjects were 1.45, 1.29, and 1.34.”

Risk of recurrent stroke in patients presenting with ischemic stroke could be predicted by the recurrence risk estimator at 90 days (RRE-90 score), according to a study in the December 16, 2009, online Neurology. Data of 1,458 patients were analyzed. Sixty recurrent strokes occurred during the follow-up period. Predictors included admission etiologic stroke subtype, prior history of TIA/stroke, topography, age, and distribution of brain infarcts. “The RRE-90 score demonstrated adequate calibration and good discrimination (area under the ROC curve (AUC), 0.70 to 0.80), which was maintained when applied to a separate cohort of 433 patients (AUC, 0.70 to 0.76),” investigators stated. “The model was also maintained for predicting early (14-day) risk of stroke.”

—Laura Sassano

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