Central nervous system manganese induced lesions and clinical consequences in patients with hereditary hemorrhagic telangiectasia.

BACKGROUND: Around 47-74% of patients with hereditary hemorrhagic telangiectasia (HHT) have hepatic vascular malformations (HVMs); magnetic resonance images (MRI) of the central nervous system (CNS) might show in T1 sequences a hyper-intensity signal in different areas, mainly in the basal ganglia (BG) as consequence of manganese (Mn) deposits as observed in cirrhotic patients. These patients might suffer from different neuropsychiatric disorders (hepatic encephalopathy). In HHT patients, even in the presence of hepatic shunts, hepatocellular function is usually preserved. Additionally, Mn shares iron absorption mechanisms, transferrin and CNS transferrin receptors. In iron deficiency conditions, the Mn may harbor transferrin and access BG. The objectives were to describe frequency of BG Mn deposit-induced lesions (BGMnIL) in HHT patients, its relationship with iron deficiency anemia (IDA) and HVMs. Finally, explore the association between neuropsychological and motor consequences. We performed a cross-sectional study. We determined HHT patients with or without BG-MnIL by the MRI screening of the CNS. We included all patients with lesions and a random sample of those without lesions. All patients underwent standardized and validated neuropsychological assessment to evaluate BG actions. Results were analyzed with multiple logistic regression, adjusting for potential confounders. RESULTS: Among 307 participants from a cohort included in the Institutional HHT Registry, 179 patients had MRI performed and Curaçao Criteria ≥3. The prevalence of BG-MnIL was 34.6% (95%CI 27.69-42.09). While neuropsychological symptoms were present in all patients, BG-MnIL patients performed poorly in three of the neuropsychological tests (serial dotting, line tracing time, number connection test A). HVMs frequency in BG-MnIL was 95.1%, versus 71.4% in those without lesions (p < 0.001). IDA frequency was 90.3% versus 54% (p < 0.001). When IDA is present, estimated risk for BG-MnIL is remarkably high (OR 7.73, 95%CI 2.23-26.73). After adjustment for possible confounders (gender, age, presence of HVMs), IDA was still associated with increased risk of BG-MnIL (adjusted OR 6.32, 95% CI 2.32-17.20; p < 0.001). CONCLUSIONS: Physicians should assess BG-MnIL in HHT patients in CNS-MRI. IDA and HVMs present increased risk of lesions. Patients with BG-MnIL have neuropsychological impairment, and they might benefit from sparing IDA, or undergoing future therapeutic options. TRIAL REGISTRATION: NCT01761981 . Registered January 3rd 2013.

ALBA Screening Instrument (ASI): A brief screening tool for Lewy Body Dementia.

BACKGROUND: Early detection of neurodegenerative diseases is essential for treatment and proper care of these patients. Screening tools available today are effective for several types of dementia. However, there is no one specific for Lewy Body Dementia (LBD). OBJECTIVES: The aim of this paper is to present a tool for early detection of LBD, accessible even for non-medical staff. METHODS: We stratified subjects (MMSE>20) into four groups: health controls (HC), Mild Cognitive Impairment (MCI), LBD and other dementias (Alzheimer and vascular). All subjects (age range 50-90) were examined with a comprehensive neuropsychological and neuropsychiatric evaluation, as well as neuroimaging to differentiate diagnosis between groups, fulfilling corresponding criteria. Both neurologists and neuropsychologists were blind to the performance on clinical evaluations and ASI, respectively. The sensitivity and specificity of the instrument were determined to differentiate LBD from other groups. RESULTS: We evaluated 427 subjects, 91 HC, 140 with MCI and 196 with dementia. In the dementia group, 75 were diagnosed with LBD and 121 with other dementias. ASI total score was 12.7±0.4 for LBD, 2.9±0.2 for HC, 5±0.7 for MCI, and 5.4±2.6 for other causes of dementia. ROC curve analysis showed a sensitivity of 90.7% and a specificity of 93.6% stands, with 9 as the cutoff with better test performance compared against other groups. CONCLUSION: ASI is a brief screening tool for LBD with high sensitivity and specificity and useful even for non-medical staff.

Previous adult attention-deficit and hyperactivity disorder symptoms and risk of dementia with Lewy bodies: a case-control study.

INTRODUCTION: previous reports have shown that in Dementia with Lewy body (DLB) and attention-deficit and hyperactivity disorder (ADHD) a hypodopaminergic and noradrenergic substrate seems to play a central role in developing the diseases. We investigated the hypothesis that attention deficit may precede DLB expressed as adult ADHD symptoms long before the clinical onset of dementia. METHODS: patients with DLB, Alzheimer disease type (ADT) and controls were recruited from the membership of the Italian Hospital Medical Care Program in Argentina from 2000 to 2005. The DSM-IV criteria adapted for the identification of adult patients with ADHD and validated to Spanish Wender Utah Rating Scale were used to identify individuals with preceding ADHD symptoms during their adult life. Analysis of categorical variables was carried out using chi-square. Mann-Whitney test was used for continuous variables. Statistical significance was P < 0.05. RESULTS: a total of 109 patients with DLB and 251 patients with ADT were matched by age, sex and year of education with 149 controls. The frequency of preceding ADHD symptoms in DLB cases was 47.8% in ADT 15.2% and 15.1% in the control group. The prevalence of ADHD symptoms in DLB cases was significantly higher compared with the control group (P ≤ 0.001, OR 5.1 95%CI 2.7-9.6) and also higher when compared with ADT (P ≤ 0.001, OR 4.9, 95%CI 2.8-8.4). CONCLUSION: we found a higher risk of DLB in patients with preceding adult ADHD symptoms. To date, there is no clear explanation for the association found; however, further investigation will widen our understanding about both disorders.

Circling seizures in a case of juvenile myoclonic epilepsy.

Circling seizures (CS) have been described in association with focal lesions as well as with generalized EEG discharges. We report 1 patient with juvenile myoclonic epilepsy (JME) who developed CS. There were no focal findings on clinical examination, EEG, or imaging studies. We propose that CS in this patient may represent a profound asymmetry in expression of an idiopathic generalized epilepsy rather than a partial condition.

Effects of monotherapy and polytherapy on the blink reflex in epileptic patients.

We performed the blink reflex (BR) in 20 normal volunteers, 13 epileptic patients receiving antiepileptic drug (AED) monotherapy, and 13 epileptic patients receiving AED polytherapy. Comparison of R1, ipsilateral and contralateral R2 and VIIth nerve latencies in the three groups showed no statistically significant differences R1 and VIIth nerve latencies among the three groups. There were statistically significant differences between the polytherapy group and the monotherapy and control groups in comparisons of ipsilateral and contralateral R2. There were no significant differences between the monotherapy group and the control group for ipsilateral and contralateral R2. We hypothesized that AED polytherapy might interfere with synaptic transmission in the polysynaptic pathway of the blink reflex, prolonging the latency of R2. These results provide further evidence of the pathophysiologic effects associated with polytherapy in epileptic patients.

Risk factors for developing seizures after a stroke.

We evaluated development of seizures in 219 consecutive patients who had ischemic or hemorrhagic stroke. Subjects with transitory ischemic attacks, subarachnoid, subdural, and epidural hemorrhages or those with previous history of epilepsy were excluded. Mean follow-up time was 11.5 months (range 1-72 months). Twenty-two of 219 stroke patients (10.04%) had seizures. Twelve (54.55%) were of early onset (< 1 month after the stroke), and 10 (45.45%) were of late onset. No statistically significant differences were evident between the early- and late-onset seizure group in comparisons of type of stroke, localization, and size of the lesion. Six of 22 patients (27%) had seizure recurrence. Seizures developed in (a) 13 of 183 patients with ischemic stroke (7.1%) and 9 of 36 patients with hemorrhagic stroke (25%) (p = 0.01); (b) 16 of 93 patients with cortical lesions (17%) and 6 of 126 patients with subcortical lesions (4.7%) (p = 0.01); and (c) 14 of 66 patients with a lesion comprising more than one lobe (21.2%) and 8 of 153 patients with a lesion comprising less than one lobe (5.2%) (p < 0.01). We conclude that patients with hemorrhagic stroke, cortical lesions, and lesions involving more than one lobe are at higher risk of developing seizures.