Clinical Significance of Delirium With Catatonic Signs in Patients With Neurological Disorders.

OBJECTIVE: According to DSM-5, catatonia and delirium are mutually exclusive clinical syndromes. The investigators explored the co-occurrence of delirium and catatonia (i.e., catatonic delirium) and the clinical significance of this syndrome with a sample of neurological patients. METHODS: This prospective study with consecutive sampling included patients diagnosed with delirium at the National Institute of Neurology and Neurosurgery of Mexico. DSM-5 criteria for delirium, the Confusion Assessment Method, and the Delirium Rating Scale-Revised-98 were used to select and characterize patients. Catatonia was assessed using the Bush-Francis Catatonia Rating Scale and DSM-5 diagnostic criteria. Logistic regression analysis was performed to identify etiological factors associated with catatonic delirium. RESULTS: A total of 264 patients with delirium were included, 61 (23%) of whom fulfilled the criteria for catatonia and delirium simultaneously. Brain tumors, subarachnoid hemorrhage, acute hydrocephalus, and ischemic stroke were associated with delirium without catatonic signs. Catatonic delirium was observed among patients with encephalitis, epilepsy, brain neoplasms, and brain tuberculosis. After multivariate analysis, the association between catatonic delirium and encephalitis (both viral and anti-N-methyl-d-aspartate receptor [NMDAR]) was confirmed. CONCLUSIONS: Delirium is a common complication of neurological diseases, and it can coexist with catatonia. The recognition of catatonic delirium has clinical significance in terms of etiology, as it was significantly associated with viral and anti-NMDAR encephalitis.

Association of Orthostatic Hypotension With Cerebral Atrophy in Patients With Lewy Body Disorders.

OBJECTIVE: To evaluate whether orthostatic hypotension (OH) or supine hypertension (SH) is associated with brain atrophy and white matter hyperintensities (WMH), we analyzed clinical and radiologic data from a large multicenter consortium of patients with Parkinson disease (PD) and dementia with Lewy bodies (DLB). METHODS: Supine and orthostatic blood pressure (BP) and structural MRI data were extracted from patients with PD and DLB evaluated at 8 tertiary-referral centers in the United States, Canada, Italy, and Japan. OH was defined as a systolic/diastolic BP fall ≥20/10 mm Hg within 3 minutes of standing from the supine position (severe ≥30/15 mm Hg) and SH as a BP ≥140/90 mm Hg with normal sitting BP. Diagnosis-, age-, sex-, and disease duration-adjusted differences in global and regional cerebral atrophy and WMH were appraised with validated semiquantitative rating scales. RESULTS: A total of 384 patients (310 with PD, 74 with DLB) met eligibility criteria, of whom 44.3% (n = 170) had OH, including 24.7% (n = 42) with severe OH and 41.7% (n = 71) with SH. OH was associated with global brain atrophy (p = 0.004) and regional atrophy involving the anterior-temporal (p = 0.001) and mediotemporal (p = 0.001) regions, greater in severe vs nonsevere OH (p = 0.001). The WMH burden was similar in those with and without OH (p = 0.49). SH was not associated with brain atrophy (p = 0.59) or WMH (p = 0.72). CONCLUSIONS: OH, but not SH, was associated with cerebral atrophy in Lewy body disorders, with prominent temporal region involvement. Neither OH nor SH was associated with WMH.

Age representation in antiepileptic drug trials: A systematic review and meta-analysis.

OBJECTIVES: To analyze age representation trends over time in antiepileptic drug (AED) trials and to assess trial design elements as possible barriers to enrollment of elderly patients. MATERIALS AND METHODS: We searched MEDLINE, EMBASE, and PsycINFO, and meta-analyzed demographic data of cohorts enrolled in randomized controlled trials (RCTs) of AEDs published since 1991. Data analysis included trends of age representation over time and trial design elements associated with average age of enrolled cohorts. RESULTS: We identified 187 studies (n = 48,077); 184 studies were included in the meta-analysis. The mean age of participants enrolled increased steadily from a mean age of 27.0 years (SD 5.7, range 21.0-38.4) in 1991-1992, to a mean age of 41.9 years (SD 11.4, range 28.8-71.4) in 2015-2016 (r = 0.868, p < 0.0001). Maximum age limit for inclusion of participants was present in 83 trials (44%). There was no significant decrease in the use of upper age limit over time (r = 0.072, p = 0.8161). Among the eligibility criteria assessed, only the exclusion of neurological conditions other than epilepsy was associated with a significant reduction of the average age of enrolled cohorts (-2.1 years, 95% CI -4.1 to -0.1). CONCLUSIONS: Despite a progressive increase in the average age of participants enrolled in AED trials over time, elderly patients are still largely underrepresented. Successful strategies to increase representation of elderly patients in these trials will likely need to involve more than minimal protocol modifications of eligibility criteria.

Peripheral lipid oxidative stress markers are related to vascular risk factors and subcortical small vessel disease.

Subcortical white matter hyperintensities (WMH), presumed to indicate small vessel ischemic vascular disease, are found commonly in elderly individuals with and without Alzheimer's disease (AD). Oxidative stress may instigate or accelerate the development of vascular disease, and oxidative stress markers are elevated in AD. Here, we assess independent relationships between three serum lipid peroxidation markers (lipid hydroperoxides [LPH], 8-isoprostane, and 4-hydroxynonenal) and the presence of extensive subcortical WMH and/or AD. Patients were recruited from memory and stroke prevention clinics into four groups: minimal WMH, extensive WMH, AD with minimal WMH, and AD with extensive WMH. Extensive WMH, but not AD, was associated with higher serum concentrations of 8-isoprostane and LPH. Peripheral LPH concentrations mediated the effect of hypertension on deep, but not periventricular, WMH volumes. 4-hydroxynonenal was associated with hyperlipidemia and cerebral microbleeds, but not with extensive WMH or AD. We conclude that lipid peroxidation mediates hypertensive injury to the deep subcortical white matter and that peripheral blood lipid peroxidation markers indicate subcortical small vessel disease regardless of an AD diagnosis.

Caffeine drinking, cigarette smoking, and dopaminergic replacement therapy dose in Parkinson's disease.

The objective of this study is to assess the effect of smoking and caffeine intake in the dosage of dopaminergic replacement therapy. Patients were recruited from the movement disorders clinic of the National Institute of Neurology and Neurosurgery in Mexico City. An interviewer-administered structured questionnaire was given to all subjects regarding their smoking and caffeine drinking habits. Dopaminergic replacement therapy information was collected and levodopa, dopamine agonists, and levodopa equivalent daily doses were calculated. 146 Parkinson's disease patients (50 % female) were included. All patients were on antiparkinsonian treatment, with a mean levodopa equivalent daily dose (LEDD) of 550.2 ± 408. Patients were stratified according to smoking and caffeine drinking status. 104 (71.2 %) of the patients were "never smokers", 33 (22.6 %) were "former smokers" and 9 (6.2 %) were "current smokers". 40 (27.4 %) patients reported no history of caffeine intake, 36 (24.7 %) were former consumers and 70 (47.9 %) were current caffeine drinkers. No association between LEDD and smoking or caffeine intake was found. A weak positive correlation (r = 0.22, p < 0.04) was found between the daily dose of pramipexole and the daily intake of caffeine. LEDD, levodopa daily dose and dopamine agonist daily dose were not related to smoking or caffeine intake status. We found a weak correlation between caffeine daily intake and pramipexole dose. Further prospective exploration is needed to address the interaction of concomitant A2A antagonism induced by caffeine intake and dopaminergic replacement therapy.

Modulation of neurotransmitter systems by dehydroepiandrosterone and dehydroepiandrosterone sulfate: mechanism of action and relevance to psychiatric disorders.

Dehydroepiandrosterone (DHEA) is synthesized in the brain and several studies have shown that this steroid is a modulator of synaptic transmission. The effect of DHEA, and its sulfate ester DHEAS, on glutamate and GABA neurotransmission has been extensively studied but some effects on other neurotransmitter systems, such as dopamine, serotonin and nitric oxide, have also been reported. This review summarizes studies showing the effect of DHEA and DHEAS on neurotransmitter systems at different levels (metabolism, release, reuptake, receptor activation), as well as the activation of voltage-gated ion channels and calcium homeostasis, showing the variety of effects that these steroids exert on those systems, allowing the discussion of its mechanisms of action and its relevance to psychiatric disorders.