A reappraisal of acute doses of benzodiazepines as a model of anterograde amnesia.

OBJECTIVE: Acute administration of benzodiazepines is considered a pharmacological model of general organic anterograde amnesias (OAA). We sought to determine which type of amnesia these drugs best model by comparing the effects of diazepam with those reported in amnesiacs regarding working memory capacity (WMC), susceptibility to retroactive interference (RI), and accelerated forgetting. METHODS: In this double-blind, parallel-group design study, 30 undergraduates were randomly allocated to acute oral treatments with 15 mg diazepam or placebo. WMC and story recall were assessed pre- and post-treatment. Story presentation was succeeded by 10 min of RI (spotting differences in pictures) or minimal RI (doing nothing in a darkened room). Delayed story recall was assessed under diazepam and 7 days later in a drug-free session to assess accelerated forgetting. RESULTS: Recall of stories encoded under diazepam, whether reactivated or not, was severely impaired (anterograde amnesia). However, diazepam did not impair WMC, increase susceptibility to RI, or accelerate forgetting. CONCLUSIONS: Diazepam's amnestic effects mirror those in patients with probable severe medial temporal damage, mostly restricted to initial consolidation and differ from other OAA (Korsakoff syndrome, frontal, transient epileptic, posttraumatic amnesia, and most progressive amnesias) in terms of WMC, susceptibility to RI and accelerated forgetting.

A Teenager With Acute Anterograde Amnesia.

Isolated amnesia is an uncommon presenting complaint in the pediatric age group. We report the case of an 18-year-old woman who presented with the acute onset of memory difficulty and an otherwise normal neurologic examination. Brain magnetic resonance imaging demonstrated inflammation in the bilateral temporal lobes. Serum and cerebrospinal fluid testing ultimately revealed a diagnosis of autoimmune encephalitis. Although rare, the acute onset of isolated amnesia deserves a prompt, comprehensive evaluation.

Development and initial validation of the alcohol-induced blackout measure.

BACKGROUND: Blackouts are common among young adults and predict alcohol-related harm. However, existing measures do not capture the range of alcohol-induced memory impairment involved in blackout experiences and do not differentiate between fragmentary and en bloc blackouts. This study aimed to develop and validate a brief, reliable measure of alcohol-induced blackouts among young adults. METHODS: College students reporting alcohol-induced memory impairment in the past year were recruited via Qualtrics to participate in an online survey (N = 350, 56% female). A subsample (n = 109, 67% female) completed a one-month follow-up. Principal component analysis was used to determine the structure of the Alcohol-Induced Blackout Measure (ABOM), which was designed to reflect two components (fragmentary and en bloc blackouts). The reliability and validity of the total ABOM score was assessed. RESULTS: The final five items fit in a two-component scale structure; however, a single principal component accounted for 73% of variance in blackout items, all of which demonstrated high component loadings and communalities. The total blackout score demonstrated strong internal consistency, test-retest reliability, and convergent and incremental validity. ABOM scores predicted alcohol-related consequences at baseline and one-month follow-up. CONCLUSIONS: The ABOM is a brief and reliable, self-report measure that quantifies the frequency of a range of blackout experiences in the past 30 days. Accounting for this range of experiences improved predictive validity over single-item blackout measures. Blackout frequency is a strong, unique predictor of alcohol-related problems.

Pure topographical disorientation in novel environments without anterograde amnesia: a case study.

Topographical disorientation (TD) in novel environments is considered to be a part of anterograde amnesia. A 56-year-old woman presented with pure TD only in novel environments following limbic encephalitis. She could not remember directions inside the hospital on weekly outpatient visits; however, her verbal and visual anterograde memories were normal. In the test of learning photographs of scenes, faces, and objects, only her scores for landscapes were worse than those in healthy controls. These findings suggested that her TD specific to landscapes and directions in novel environments was caused by category-specific memory impairment related to bilateral hippocampal and parahippocampal dysfunction.

Transient epileptic and global amnesia: Real-life differential diagnosis.

OBJECTIVE: Transient epileptic amnesia (TEA) is an underestimated condition in emergency clinical setting, where most of transient amnesic episodes tend to be classified as transient global amnesia (TGA). We designed this study to evaluate the actual frequency of TEA in a real-life scenario and to highlight the features that can help clinicians distinguishing it from TGA. METHODS: We retrospectively collected clinical data of 83 patients who accessed our emergency ward for an abrupt onset of amnesic disorder, initially interpreted as TGA. All patients underwent neurological evaluation, magnetic resonance imaging (MRI) scan, and standard 21-channel scalp electroencephalography (EEG) recording (standard EEG [st-EEG]). Moreover, patients with borderline epileptiform abnormalities on st-EEG or with normal st-EEG but high clinical suspicion for TEA underwent a 16-channel 24-hour ambulatory EEG (24-h EEG). Clinical features, neurophysiological, and neuroimaging data were analyzed and compared in the two groups (TEA and TGA). RESULTS: Diagnosis of TEA, according to Zeman's criteria, was made in 15 patients (18%). From a clinical point of view recurrence (p < .001) and atypical symptoms such as confusion or language disorder (TGA plus manifestations), appear to be key elements in order to discriminate between TEA and TGA (80% of patients with TEA vs 7.8% of patients with TGA; p < .001). In our sample, duration of the episodes did not significantly differ between TGA and TEA, even though it is usually described as shorter for TEA. This result could be related with a prolonged postictal state in these patients. The analysis of st-EEG results evidenced low sensitivity for interictal epileptiform abnormalities (IEAs) detection (52.3%), with not conclusive data in distinguishing TEA from TGA. On the contrary, 24-h EEG showed IEAs in all patients with epilepsy, mostly during sleep, suggesting an essential diagnostic role of long-lasting EEG recording for TEA. Finally, structural abnormalities were more frequent in patients with TEA (26.6%). In the group with TGA, the only imaging alteration found was diffusion weighted imaging (DWI) hippocampal hyperintensity. CONCLUSION: Our findings show that in a real-life clinical scenario, TEA is frequent but often overlooked. However, simple clinical data and widely available neurophysiological examinations can truly help to effectively distinguish TEA from TGA.

Utility of Retrograde Amnesia Assessment Alone, Compared with Anterograde Amnesia Assessment in Determining Recovery After Traumatic Brain Injury: Prospective Cohort Study.

BACKGROUND: Posttraumatic amnesia (PTA) after traumatic brain injury (TBI) comprises anterograde amnesia (AA), disorientation, and retrograde amnesia (RA). However, RA is often neither assessed nor emphasized. A recent study demonstrated that although AA and disorientation were both present in non-TBI inpatients uniformly taking opioids, RA was absent. This suggests potentially significant utility with RA assessment alone since opioids are commonly prescribed post TBI. METHODS: We compared RA recovery with AA recovery in a prospective cohort post TBI. The Galveston Orientation and Amnesia Test (GOAT) represented a crude test for PTA (GOAT <75). AA was primarily assessed using the Westmead PTA Scale, and RA was assessed using the GOAT. All patients were prescribed oxycodone. RESULTS: Results were obtained (n = 31). While RA recovery coincided with a GOAT recovery in 19/31 (61%), AA recovery coincided with GOAT recovery in only 6/31 (19%), (χ2 = 11.5, P < 0.001). RA recovery preceded AA recovery in 15/31 (48%), while AA recovery preceded RA recovery in 7/31 (23%) (χ2 = 8.6, P = 0.003). Where RA recovery less frequently followed AA recovery, temporal lobe contusions were more frequent. RA recovery preceded/coincided with AA recovery in 100% of those who recovered when AA was defined as ×3 consecutive 12/12 scores (as is current widespread practice). AA recovery typically followed RA recovery with minimal delay. CONCLUSIONS: In the presence of potential in-hospital confounders including opioids, RA recovered significantly sooner after TBI than AA and was predictive of imminent AA recovery. RA assessment alone therefore had significant and novel utility in post-TBI assessment. RA assessment should be routinely recorded in all PTA assessment. Given its simplicity and resilience to common confounders, RA assessment should also be incorporated into the Glasgow Coma Scale.

An association of cognitive impairment with diabetes and retinopathy in end stage renal disease patients under peritoneal dialysis.

BACKGROUND: Diabetes and retinopathy have been considered as risk factors of cognitive impairment (CI) in previous studies. We investigated both of these two factors and their relationship with global and specific cognitive functions in end stage renal disease patients under peritoneal dialysis (PD). METHODS: In this multicenter cross-sectional study, 424 clinically stable patients were enrolled from 5 PD units, who performed PD for at least three months and completed fundoscopy examination if they had diabetes. Global cognitive function was measured using the Modified Mini-Mental State Examination (3MS), Trail-Making Test forms A and B for executive function, and subtests of the Battery for the Assessment of Neuropsychological Status for immediate and delayed memory, visuospatial skills, and language ability. RESULTS: PD Patients with DM and Retinopathy had significantly higher prevalence of CI, executive dysfunction, impaired immediate memory and visuospatial skill, compared with patients in non-DM group. By multivariate logistic regression analyses, DM and retinopathy rather than DM only were significantly associated with increased risk for CI, executive dysfunction, impaired immediate memory and visuospatial skill, odds ratios(ORs) and 95% confidence intervals were 2.09[1.11,3.92], 2.89[1.55,5.37], 2.16 [1.15,4.06] and 2.37[1.32,4.22], respectively (all P < 0.05). CONCLUSIONS: Diabetic PD patients with retinopathy were at two times risk for overall cognitive impairment, executive dysfunction, impaired immediate memory and visuospatial skill as compared to non-diabetic PD patients.

Anterograde amnesia and disorientation are associated with in-patients without traumatic brain injury taking opioids. Retrograde amnesia (RA) is absent. RA assessment should be integral to post-traumatic amnesia testing.

The Glasgow Coma Scale (GCS) only assesses orientation after traumatic brain injury (TBI). 'Post-traumatic amnesia' (PTA) comprises orientation, anterograde amnesia (AA) and retrograde amnesia (RA). However, RA is often disregarded in formalized PTA assessment. Drugs can potentially confound PTA assessment: e.g. midazolam can cause AA. However, potential drug confounders are also often disregarded in formalized PTA testing. One study of medium-stay elective-surgery orthopaedic patients (without TBI) demonstrated AA in 80% taking opiates after general anesthesia. However, RA was not assessed. Opiates/opioids are frequently administered after TBI. We compared AA and RA in short-stay orthopaedic surgery in-patients (without TBI) taking post-operative opioids after opiate/opioid/benzodiazepine-free spinal anesthesia. In a prospective cohort, the Westmead PTA Scale (WPTAS) was used to assess AA (WPTAS<12), whilst RA was assessed using the Galveston Orientation and Amnesia Test RA item. Results were obtained in n=25 (60±14yrs, M:F 17:8). Surgery was uncomplicated: all were discharged by Day-4. All were taking regular oxycodone as a new post-operative prescription. Only one co-administered non-opioid was potentially confounding (temezepam, n=4). Of 25, 14 (56%) demonstrated AA: five (20%) were simultaneously disorientated. Mean WPTAS was 11.08±1.22. RA occurred in 0%. CONCLUSIONS: AA and disorientation, but not RA, were associated with in-patients (without TBI) taking opioids. Caution should therefore be applied in assessing AA/orientation in TBI in-patients taking opioids. By contrast, retrograde memory was robust and more reliable: even in older patients with iatrogenic AA and disorientation. RA assessment should therefore be integral to assessing TBI severity in all formalized PTA and GCS testing.

What is the level of evidence for the amnestic effects of sedatives in pediatric patients? A systematic review and meta-analyses.

BACKGROUND: Studies have suggested that benzodiazepines are amnestic drug par excellence, but when taken together, what level of evidence do they generate? Are other sedatives as amnestic as benzodiazepines? The aim of this study was to assess the level of scientific evidence for the amnestic effect of sedatives in pediatric patients who undergo health procedures. METHODS: The literature was searched to identify randomized controlled trials that evaluated anterograde and retrograde amnesia in 1-19-year-olds who received sedative drugs during health procedures. Electronic databases, including PubMed, Scopus and Cochrane Library besides clinical trial registries and grey literature were searched. Two independent reviewers performed data extraction and risk of bias assessment using the Cochrane Collaboration's Tool. The meta-analyses were performed by calculating relative risk (RR) to 95% confidence intervals (CI). The quality of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Fifty-four studies were included (4,168 participants). A higher occurrence of anterograde amnesia was observed when benzodiazepines, the most well-studied sedatives (n = 47), were used than when placebo was used (n = 12) (RR = 3.10; 95% CI: 2.30-4.19, P<0.001; I2 = 14%), with a moderate level of evidence. Higher doses of alpha2-adrenergic agonists (clonidine/dexmedetomidine) produced more anterograde amnesia than lower doses (n = 2) (RR = 1.83; 95% CI: 1.03-3.25; P = 0.038; I2 = 0%), with a low level of evidence; benzodiazepines' amnestic effects were not dose-dependent (n = 3) (RR = 1.54; 95% CI: 0.96-2.49; P = 0.07; I2 = 12%) but the evidence was low. A qualitative analysis showed that retrograde amnesia did not occur in 8 out of 10 studies. CONCLUSIONS: In children, moderate evidence support that benzodiazepines induce anterograde amnesia, whereas the evidence for other sedatives is weak and based on isolated and small studies. Further clinical trials focused on the amnesia associated with non-benzodiazepine sedatives are therefore needed. TRIAL REGISTRATION: PROSPERO CRD42015017559.

Transient global amnesia in immediate postoperative period: A diagnostic dilemma.

INTRODUCTION: Transient Global Amnesia (TGA) is short-term inability to form new memories despite otherwise normal neurological function. There is associated anterograde and retrograde amnesia. The memory loss is often accompanied by repetitive questioning and temporal disorientation while higher cognitive functions are preserved. The symptoms usually resolve by 24h. CASE REPORT: We present an interesting case of 31year old female who was planned for robotically assisted right sided pyeloplasty. 30min after emergence from anaesthesia patient was disoriented, with retrograde and anterograde amnesia, but neurological function was intact. Neurologic imaging revealed no abnormality. 36h later patient was able to recall everything. DISCUSSION: The pathogenesis of TGA has more recently been attributed to cerebral venous hypertension resulting from retrograde jugular venous flow. Precipitating events are Valsalva manoeuvre, emotion/stress/pain, Excessive exertion, sexual intercourse and swimming in cold water. CONCLUSION: TGA presents dramatically, it needs to be differentiated from cerebral event. It resolves on its own. But one needs to be aware of existence of such an entity.

A rare case of aortic dissection presenting as pure transient global amnesia.

Transient global amnesia (TGA) is a well-described neurological phenomenon. Clinically, it manifests with the sudden onset of a paroxysmal, transient loss of anterograde memory and disorientation but with intact consciousness. Typically, symptoms last for only a few hours. We present an unusual case of aortic dissection presenting with pure TGA in a patient, who had a positive outcome. This is the second case report of a patient with aortic dissection presenting with pure TGA syndrome, but it is the first case in which the patient survived.

Neuropsychiatric Manifestations of Colloid Cysts: a review of the literature.

Colloid cysts account for approximately 2% of primary brain tumours and the majority of cases are identified in the fourth and fifth decade. They are small, gelatinous neoplasms lined by a single layer of mucin-secreting columnar epithelium that are thought to arise from errors in folding of the primitive neuroepithelium. They develop in the rostral aspect of the third ventricle in the foramen of Monro in 99% of cases and despite their benign histology carry a poor prognosis, with a mortality greater than 10% in symptomatic cases. The location of colloid cysts within the ventricular system results in obstruction of the foramen of Monro as the cyst grows, disrupting the circulation of cerebrospinal fluid (CSF) and causing hydrocephalus. This is the mechanism behind the most common presenting symptoms of postural headache, nausea and vomiting - a clinical picture synonymous with hydrocephalus and intracranial pathology. In addition to these classical neurological symptoms, there is a high prevalence of psychiatric symptoms in the patient population, with symptoms ranging from anterograde amnesia to gustatory hallucination. These symptoms can occur with or without the presence of hydrocephalus, and are thought to be secondary to compression of connecting pathways between the mesocortices and subcortical limbic regions. These symptoms have been shown to be comparative in frequency to the classical symptoms, yet are rarely the reason for referral to a neurological or neurosurgical service for investigation.

Cognitive side-effects of electroconvulsive therapy in elderly depressed patients.

Knowledge about cognitive side-effects induced by electroconvulsive therapy (ECT) in depressed elderly patients is sparse. In this study we investigated changes in the cognitive functioning of non-demented elderly depressed patients receiving ECT (n = 62) compared with healthy elderly people (n = 17). Neuropsychological tests were administered at the start of treatment and again within 1 week after treatment. We computed reliable change indices (RCIs) using simple regression methods. RCIs are statistical methods for analyzing change in individuals that have not yet been used in studies of the acute cognitive side-effects of ECT. At the group level, only letter fluency performance was found to be significantly reduced in the ECT group compared with the controls, whereas both groups demonstrated stable or improved performance on all other measures. At the individual level, however, 11% of patients showed retrograde amnesia for public facts post-ECT and 40% of the patients showed a significant decline in neuropsychological functioning. Decline on a measure of delayed verbal anterograde memory was most common. Our findings indicate that there are mild neurocognitive impairments in the acute phase for a substantial minority of elderly patients receiving ECT. Analysis of reliable change facilitated the illumination of cognitive side-effects in our sample.

Clinical, neuropsychological, and metabolic characteristics of transient epileptic amnesia syndrome.

OBJECTIVE: Transient epileptic amnesia (TEA) is a recently individualized syndrome occurring in adult patients that includes epileptic seizures with amnestic features and interictal memory disturbances. METHODS: We investigated the clinical, neuropsychological, and 18F-FDG positron emission tomography (18F-FDG-PET) features of 30 consecutive cases of TEA in our center. RESULTS: The mean age of onset of amnestic seizures was 59 years. Pure acute amnesia was the only epileptic manifestation in 17% of cases. Interictal electroencephalography (EEG) abnormalities were present in 57% on awake recording and in most patients in whom sleep EEG was performed (96%). Nine of 30 patients showed anterograde memory deficit and six of 30 exhibited mild executive functioning impairment. On the autobiographical memory interview (AMI), patients showed a significant deficit for the recent period of the episodic subscale. Outcome under treatment was favorable in the majority of cases. A significant improvement was noted on recollection of autobiographical memory. 18F-FDG-PET (22 cases) showed positive correlations between left mesial temporal metabolism levels and anterograde and retrograde memory scores. SIGNIFICANCE: TEA is an emerging epileptic syndrome that likely remains misidentified and misdiagnosed. Neurometabolic data support a dysfunction of a hippocampal-neocortical network sustaining episodic memory.