"iDoctor – Medical Blog"

Cognitive impairment and seizures are common in our aging population. Anticonvulsant treatment is problematic due to sedation, cognitive slowing, and behavioral changes. Levetiracetam has favorable pharmacokinetics, good efficacy in elderly individuals, a favorable side effect profile, and lacks major drug interactions. We conducted a prospective, uncontrolled, phase 4, open label, 12-week study of levetiracetam to better profile its efficacy, safety, and impact on cognitive/behavioral status in 24 cognitively impaired, elderly individuals. In total, 69% were seizure free for the duration of the study; the remaining participants had satisfactory seizure control. Fatigue was the most common side effect (5 participants). Significant overall improvements were observed for the Folstein’s Mini-Mental State Examination and the Alzheimer’s Disease Assessment Scale—Cognitive. No significant changes were seen in behavioral or functional measures. Levetiracetam is an effective antiepileptic drug in elderly individuals with cognitive impairment. At 3 months, participants who remained on levetiracetam showed excellent cognitive tolerability.

Following a 48-week, double-blind, randomized, placebo-controlled trial of donepezil in 821 patients with amnestic mild cognitive impairment (aMCI), safety and tolerability of donepezil (10 mg) were further evaluated in a 28-week extension study. Of 499 participants who completed the double-blind phase, 145 enrolled in the open-label study. Adverse events (AEs) were recorded throughout. Overall, 57.4% of participants in the donepezil/donepezil group and 62.3% in the placebo/donepezil group experienced an AE, with the most frequent treatment-emergent AEs being diarrhea, muscle spasms, insomnia, and nausea. Most were mild to moderate in severity and were more common in the first several weeks after treatment initiation. More participants in the placebo/donepezil group (22.1%) discontinued donepezil due to an AE compared with the donepezil/donepezil group (10.3%). These findings support the safety of donepezil in patients with aMCI. When compared with other studies, however, the data suggest that patients with Alzheimer’s tolerate donepezil better than patients with MCI.

Objective: The purpose was to describe (a) individuals’ reasons for participating in cognitive screening and (b) reasons to pursue testing after screening across 4 ethnic groups: African American, Afro-Caribbean, European American, and Hispanic American. Methods: Prior to memory screening, 119 adults were interviewed regarding their thoughts about memory screening and follow-up testing. Interviews were coded and differences between ethnic groups were compared. Results: More African Americans and European Americans were concerned about their memory. More Hispanic Americans planned to seek professional help if needed. Hispanic Americans were most optimistic about treatment. Conclusions: Future research is needed to better understand cultural factors that influence older adults’ willingness to be screened for cognitive impairment and to pursue follow-up testing when recommended.

Wandering is a complex behavior, and defining wandering has been challenging. The current study used the integrated circuit (IC) tag monitoring system to describe the distance moved per day and the spatial movements of patients with dementia. The study was conducted in a 60-bed semiacute dementia care unit in a general hospital in Japan over a 3-month period in 2006. The distance moved per day, the numbers of pacing and lapping movements, and the proportions of the distance moved that was paced or lapped were tabulated in 23 patients diagnosed with dementia. The distance moved per day and the numbers of pacing and lapping movements varied greatly within and among study participants. The median distance moved per day was inversely correlated with participants’ age and Mini-Mental State Examination (MMSE) scores (adjusted r² = .34, P = .01). Consecutive lapping and pacing movements were rare patients with in Alzheimer’s disease (AD), while 2 patients with frontotemporal dementia paced or lapped repeatedly.

Auriel E, Bornstien NM, Berenyi E, Varkonyi I, Gabor M, Majtenyi K, Szepesi R, Goldberg I, Lampe R, Csiba L. Clinical, radiological and pathological correlates of leukoaraiosis. Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2010.01341.x. © 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Introduction – Leukoaraiosis is characterized by an abnormal appearance of the brain white matter on imaging. Its pathogenesis is still a matter of investigation. The purpose of this study was to investigate the radiological, clinical and pathological correlates of leukoaraiosis. Methods – The study population consisted of 93 deceased patients. The pre-mortem T2W magnetic resonance images were evaluated for the presence and grading of leukoaraiosis. The clinical and pathological characteristics based on the clinical charts and autopsy reports were evaluated. Tissue specimens of the blocks of 19 brains that demonstrated severe leukoaraiosis and those of five control brains were excised and stained. Results – The variables found to be significantly associated with leukoaraiosis were age and a clinical history of Parkinson’s disease. Other risk factors and pathological markers of atherosclerosis were not significantly correlated with leukoaraiosis. No significant difference was found between the scoring of the myelin integrity, glial fibrillary acidic protein, cluster of differentiation 68 and smooth muscle actin. There was a significant difference with respect to thickening of vessels walls. Conclusions – Our pathological results indicate that structural vascular abnormalities characterized by vessel wall thickening are associated with leukoaraiosis, supporting the assertion that vascular changes and ischemia generate leukoaraiosis. The relations between parkinsonism and leukoaraiosis may be explicable through vascular effects on the circuitry of the basal ganglia.

Piña-Garza JE, Schwarzman L, Wiegand F, Hulihan J. A pilot study of topiramate in childhood absence epilepsy. Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2010.01347.x. © 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard.Objective [ndash] Evaluate the antiepileptic effect of topiramate monotherapy in childhood absence epilepsy (CAE).Materials and Methods [ndash] Childhood absence epilepsy patients aged 4[ndash]9 years were initiated with topiramate 15 or 25 mg/day, which was titrated upwards until patients were free of absence seizures. The primary efficacy outcome was seizure-free rates after a 12-week maintenance period.Results [ndash] The study was terminated early due to lack of efficacy after enrollment of 12 patients. Four patients completed the study; two became clinically seizure-free, but without a significant reduction in the number of electrographic seizures. Six patients discontinued for lack of efficacy, none due to adverse events (AEs). Mean reduction in seizure count was seen on Days 22 (P = 0.0391) and 36 (P = 0.0156) and percentage of days with seizures decreased from baseline. Most AEs were mild.Conclusions [ndash] Although well-tolerated, this pilot study did not demonstrate an antiepileptic effect of topiramate monotherapy for treatment of CAE.

Lindekleiv HM, Njølstad I, Ingebrigtsen T, Mathiesen EB. Incidence of aneurysmal subarachnoid hemorrhage in Norway, 1999[ndash]2007. Acta Neurol Scand: DOI: 10.1111/j.1600[ndash]0404.2010.01336.x. © 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard.Objective [ndash] To investigate changes and regional variations in annual incidence rates of aneurysmal subarachnoid hemorrhage (SAH) in Norway between 1999 and 2007.Methods [ndash] The authors retrospectively reviewed data from the Norwegian Patient Register for the period 1999[ndash]2007.Results [ndash] Crude incidence of aneurysmal SAH was 10.0/100,000 person years [95% CI (confidence interval): 9.7[ndash]10.3] and was higher in women (12.0/100,000 person years; 95% CI: 11.5[ndash]12.5) than men (8.1/100,000 person years; 95% CI: 7.7[ndash]8.4). Decreasing annual incidence rates were observed from 11.1/100,000 person years (95% CI: 10.5[ndash]11.6) in the period 1999[ndash]2001 to 8.9/100,000 person years (95% CI: 8.4[ndash]9.4) in the period 2005[ndash]2007 (P for trend <0.001). Regional variations were observed, from 8.4/100,000 person years (95% CI: 7.7[ndash]9.00) in the southern region, 10.4/100,000 person years (95% CI: 9.5[ndash]11.2) in the central region and 11.9/100,000 person years (95% CI: 10.8[ndash]12.9) in the northern region.Conclusions [ndash] Incidence of aneurysmal SAH in Norway decreased from 1999 to 2007, with significant regional variations indicating an increasing gradient from south to north.

Rentzos M, Rombos A, Nikolaou C, Zoga M, Zouvelou V, Dimitrakopoulos A, Alexakis T, Tsoutsou A, Samakovli A, Michalopoulou M, Evdokimidis J. Interleukin-17 and interleukin-23 are elevated in serum and cerebrospinal fluid of patients with ALS: a reflection of Th17 cells activation?Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2010.01333.x.© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard.Background [ndash] There is evidence that immunological factors may involved in pathogenetic mechanisms of amyotrophic lateral sclerosis (ALS). Th17 cells are characterized by predominant production of IL-17 and are suggested to be crucial in destructive autoimmunity. Interleukin-23 (IL-23) appears to play a supporting role in the continued stimulation and survival of Th17.Patients and methods [ndash] We measured by enzyme-like immunosorbent assay (ELISA) serum and cerebrospinal fluid (CSF) levels of IL-17 and IL-23 in 22 patients with ALS and 19 patients with other non-inflammatory neurological disorders (NIND) studied as a control group. IL-17 and IL-23 serum and CSF levels were also correlated with duration of the disease, the disability level and the clinical subtype of the disease onset in patients with ALS.Results [ndash] IL-17 and IL-23 serum levels were higher in patients with ALS as compared with patients with NIND (P = 0.015 and P = 0.002 respectively). IL-17 and IL-23 CSF levels were also increased in patients with ALS (P = 0.0006 and P = 0.000001 respectively). IL-17 and IL-23 levels were not correlated with disease duration, disability scale or clinical subtype of the disease onset in ALS patients.Conclusions [ndash] Our findings suggest that these molecules may be involved in the pathogenetic mechanisms acting as potential markers of Th17 cells activation in ALS.