Severe Memory Disturbance Research Articles

High-Dose Benzodiazepine Users' Perceptions and Experiences of Anterograde Amnesia.

Associations between criminal activity and the use of psychotropic substances are well established. Flunitrazepam, specifically, has been suspected of triggering, per se, violent criminal behavior and severe memory disturbances in the form of anterograde amnesia. However, data from investigations of this relationship are scarce and have been primarily derived from forensic institutions, where there may be a reporting bias. This study was a qualitative exploration of high-dose benzodiazepine users' experiences of anterograde amnesia symptoms and their beliefs about their behavior during the phases of memory impairment in a nonforensic setting. Users subjectively reported experiencing symptoms of anterograde amnesia, especially after combining short-acting benzodiazepines with alcohol, but only rarely when using slow-onset, long-acting compounds. They perceived their experiences as unpleasurable, unpredictable, and embarrassing. Their awareness developed with time, triggered by descriptions of disinhibited and erratic behavior by others. Users described being victimized during phases of anterograde amnesia in addition to engaging in violent and criminal activities themselves. Although unable to recall, many participants believed that they had been able to make rational decisions while intoxicated with flunitrazepam, disregarding notions of diminished insight. In light of the varying terminology used for the phases of memory disturbance and these findings, we suggest that forensic experts additionally explore evaluees' beliefs about amnestic periods and their self-perceptions about their behaviors during these episodes, when evaluating high-dose benzodiazepine-dependent patients.

Dress syndrome associated autoimmune limbic encephalitis with epstein–barr virus reactivation

Introduction: Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe drug hypersensitivity reaction characterized by rash, fever and multi-organ failure. The most frequent causative drugs are the antiepileptics and antimicrobials. Recent studies demonstrated that some viruses can be reactivated during the course of this syndrome. Limbic encephalitis is a rare disorder characterized by cognitive dysfunction with severe memory disturbance, seizures, and psychiatric symptoms. We present a case of DRESS syndrome with reactivation of EBV who developed autoimmune limbic encephalitis.

Arachnoid cyst of the velum interpositum originating from tela choroidea

Background:Arachnoid cysts originating from the velum interpositum are very rare, and their existence as a clinicopathologic entity remains controversial. We report a case of a patient with an arachnoid cyst of the velum interpositum presenting with memory disturbance, focusing on the anatomical origin of the lesion and the physiological mechanisms causing memory disturbance.Case Description:A 65-year-old man with a large cystic lesion in the velum interpositum experienced progressive memory disturbance and enlargement of the lesion 6 months before referral to our institution. Neuropsychological evaluation on admission demonstrated severe memory disturbance. Radiological examination did not reveal hydrocephalus, but the bilateral fornices and thalami were compressed by the cyst. The patient underwent endoscopic cystoventriculostomy via the frontal horn of the right lateral ventricle through a frontal burr hole. Histopathology of the sample was consistent with that of an arachnoid cyst, and the endoscopic findings suggested that the cyst originated from the tela choroidea, which covers the velum interpositum. The symptoms resolved after surgery with significant improvement in neuropsychological test scores.Conclusion:Arachnoid cysts of the velum interpositum are rare but distinct clinicopathologic entities that originate from the tela choroidea. The lesions can cause memory disturbance without hydrocephalus due to compression of the fornices and thalami, but this can be reversed by surgery.

Astrocytes support hippocampal-dependent memory and long-term potentiation via interleukin-1 signaling

Recent studies indicate that astrocytes play an integral role in neural and synaptic functioning. To examine the implications of these findings for neurobehavioral plasticity we investigated the involvement of astrocytes in memory and long-term potentiation (LTP), using a mouse model of impaired learning and synaptic plasticity caused by genetic deletion of the interleukin-1 receptor type I (IL-1RI). Neural precursor cells (NPCs), derived from either wild type (WT) or IL-1 receptor knockout (IL-1rKO) neonatal mice, were labeled with bromodeoxyuridine (BrdU) and transplanted into the hippocampus of either IL-1rKO or WT adult host mice. Transplanted NPCs survived and differentiated into astrocytes (expressing GFAP and S100β), but not to neurons or oligodendrocytes. The NPCs-derived astrocytes from WT but not IL-1rKO mice displayed co-localization of GFAP with the IL-1RI. Four to twelve weeks post-transplantation, memory functioning was examined in the fear-conditioning and the water maze paradigms and LTP of perforant path-dentate gyrus synapses was assessed in anesthetized mice. As expected, IL-1rKO mice transplanted with IL-1rKO cells or sham operated displayed severe memory disturbances in both paradigms as well as a marked impairment in LTP. In contrast, IL-1rKO mice transplanted with WT NPCs displayed a complete rescue of the impaired memory functioning as well as partial restoration of LTP. These findings indicate that astrocytes play a critical role in memory functioning and LTP, and specifically implicate astrocytic IL-1 signaling in these processes. The results suggest novel conceptualization and therapeutic targets for neuropsychiatric disorders characterized by impaired astrocytic functioning concomitantly with disturbed memory and synaptic plasticity.

Aripiprazole, Hypertension, and Confusion

To the Editor: Aripiprazole is a sec- ond-generation antipsychotic approved for schizophrenia and for the treatment of mania and mixed episodes associated with bipolar disorder. Aripiprazole has also been approved for the treatment of major depressive disorder in adults as an add-on therapy. Aripiprazole exhibits a high affinity for dop- reuptake inhibitors. She also received augmentation strategies such as lithium, olanzapine, and dopaminergic agonists. Tolerance associated with all these therapeu- tics was always excellent. Unfortu- nately, she never achieved remis- sion state. Ten years earlier, she underwent a coronary artery bypass graft surgery without any complications. She was treated for many years with low doses of aspi- rin, pravastatin, and bisoprolol for a moderate hypertension, and she was considered by cardiologists to be very well stabilized. She was treated with venlafaxine, 150 mg, without problems of hypertension related to the medication, and we decided to add aripiprazole, 5 mg, to potentiate the antidepressant effect of venlafaxine. About 48 hours after the first intake of aripi- prazole, she became confused with symptoms such as loss of orienta- tion, severe memory disturbances, and agitation. An arterial hyperten- sion of 200/110 mmHg was mea- sured, and the ECG was normal except for tachycardia (110 bpm). We decided to discontinue aripi- prazole, and both hypertension and confusion resolved over 48 hours without treatment. The patient had never presented such symptomatol- ogy before. Over a period of 1 year, without addition of any new antihypertensive medication, and with venlafaxine treatment main- tained during 4 months, the patient never experienced confusion again, and her blood pressure remained below 150/90 mmHg.

Neuropsychological Improvement in Patients With Cervical Spondylotic Myelopathy After Posterior Decompression Surgery

Patients with cervical spondylotic myelopathy sometimes complain of cognitive dysfunction, which may be coincidence. However, cognitive dysfunction may be related to disorders of the cervical spine and/or spinal cord. This study investigated cognitive dysfunction in patients with cervical spinal disorders. A total of 79 patients with cervical spondylotic myelopathy (40 women and 39 men, mean age 61.2 years) underwent cervical laminoplasty between January 2006 and July 2007. Ten of these 79 patients (7 women and 3 men, mean age 65.2 years) complained of moderate to severe memory disturbances. These 10 patients underwent neuroimaging studies and a battery of neuropsychological tests consisting of the mini-mental state examination, Kohs Block Design Test, Miyake Memory Test, Benton Visual Retention Test (BVRT), and "kana-hiroi" test before and 3 months after surgery. Brain magnetic resonance imaging showed no organic brain lesions in the 10 patients, but single photon emission computed tomography demonstrated reduced regional cerebral blood flow in the posterior cortical areas in eight patients before surgery. Neuropsychological test scores showed statistically significant improvement after surgery in the Kohs Block Design Test and the BVRT, which measure visuospatial perception and reflect the function of the parietal and/or occipital lobes (p < 0.05). The practice effect may have contributed to the neuropsychological improvements, but this study suggests that cervical spinal disorders may affect cognitive functions and that surgical treatment can ameliorate such effects.

左内側後頭頭頂葉病変で発症したｐｏｓｔｓｔｒｏｋｅ ｄｅｍｅｎｔｉａの１例

We report herein a patient of poststroke dementia (PSD) following left medial occipitoparietal hemorrhage triggered by drainage of an acute traumatic subdural hematoma. The patient, an independent 73-year-old man, became dependent due to dementia. Cognitive dysfunction was characterized by moderately decreased IQ, severe memory disturbances, topographical disorientation, executive dysfunction and loss of self-awareness. Cognitive dysfunction has not advanced for 3 years. Hypo-perfusion in the whole brain, particularly in the left temporal and parietal regions, was visible on 123I-IMP SPECT images. Magnetic resonance imaging demonstrated damage to the left posterior cingulate cortex, cingulate bundle, superior parietal lobule and subcortical region of the occipital lobe. The fornix was spared. Some subcortical small spotted lesions were detected, but periventricular lucency was not prominent. Structures known to be important in memory but spared by the lesion included the thalamus and basal forebrain. Small spotted subcortical lesions were detected in bilateral hippocampi, which are also known to be important in memory, but these were probably silent lesions. This case suggested that dementia is brought on by the lesion of the left posterior cingulate bundle and retrosplenial cortex causing amnesia by disrupting the cingulate-hippocampal connection or the retrosplenial cortex itself, with the lesion of the left occipitoparietal subcortex causing frontal dysfunction by disrupting the dorsal limbic pathway and occipitofrontal fasciculus of the prefrontal circuits.

Selective anterograde amnesia with thalamus and hippocampal lesions in neuro-Behcet's disease

Anterograde amnesia and minimal retrograde amnesia with thalamic and hippocampal lesions in neuro-Behcet's disease is rare. A 50-year-old man presented with forgetfulness and severe memory disturbance after suffering multiple oral and genital aphthous ulcers with erythema nodosum. A neurological examination and a neuropsychological assessment revealed prominent anterograde memory impairment without focal neurological deficits. On brain MRI there were high signal intensity lesions involving right anterior thalamus, left posterior basal ganglia, and left hippocampus. This is a quite selective anterogrde memory deficit in a case of neuro-Behcet's disease caused by parenchymal lesions in the thalamus and hippocampus.

Who's Afraid of Status Epilepticus?

Who's Afraid of Status Epilepticus?

Genetic ablation of the mammillary bodies in the Foxb1 mutant mouse leads to selective deficit of spatial working memory

Mammillary bodies and the mammillothalamic tract are parts of a classic neural circuitry that has been implicated in severe memory disturbances accompanying Korsakoff's syndrome. However, the specific role of mammillary bodies in memory functions remains controversial, often being considered as just an extension of the hippocampal memory system. To study this issue we used mutant mice with a targeted mutation in the transcription factor gene Foxb1. These mice suffer perinatal degeneration of the medial and most of the lateral mammillary nuclei, as well as of the mammillothalamic bundle. Foxb1 mutant mice showed no deficits in such hippocampal-dependent tasks as contextual fear conditioning and social transmission of food preference. They were also not impaired in the spatial reference memory test in the radial arm maze. However, Foxb1 mutants showed deficits in the task for spatial navigation within the Barnes maze. Furthermore, they showed impairments in spatial working memory tasks such as the spontaneous alternation and the working memory test in the radial arm maze. Thus, our behavioural analysis of Foxb1 mutants suggests that the medial mammillary nuclei and mammillothalamic tract play a role in a specific subset of spatial tasks, which require combined use of both spatial and working memory functions. Therefore, the mammillary bodies and the mammillothalamic tract may form an important route through which the working memory circuitry receives spatial information from the hippocampus.

Relations Among Indexes of Memory Disturbance and Depression in Patients With Lyme Borreliosis

This study examined the relation between complaints of memory disturbance and measures of mood and memory functioning in 55 patients with serological evidence of late-stage Lyme Borreliosis (LB). Patients completed the Self-Ratings of Memory Questionnaire (SRMQ) and the Beck Depression Inventory. Memory functioning was assessed with the California Verbal Learning Test. Depressed patients exhibited more frequent complaints of memory disturbance on the SRMQ, although their pattern of responses did not differ from nondepressed patients. There was a significant correlation between subjective memory ratings and self-reported depression (Spearman p = -.57, p < .001). No relation was observed between subjective memory ratings and objective memory performance. The results indicate subjective complaints of more severe memory disturbance inpatients with LB and depression. Particular attention should be paid to the assessment of depression and subjective symptoms of memory disturbance when administering neuropsychological tests of memory functioning in patients with LB.

A new type of epidemiological study: questionnaire administered by medical personnel.

Doctors, nurses, and medical and nursing students administered a questionnaire on memory disturbances, tremor and clumsiness in their first-degree relatives who live or lived near them. We obtained data on 1,479 relatives, of whom 805 were alive and 674 had died. Of those alive and older than 65, 8.69% had severe memory disturbances, 1.11% a parkinsonian syndrome and 5.59% essential tremor. Of those who had died, 10.68% had suffered from severe memory disturbances before they died. The results of both groups are similar and in accordance with the data in the literature. In our opinion this new type of epidemiological study can be very useful in diseases which are easily detected by nonspecialists and in areas with hospitals and medical schools.

The use of a computer in aiding functional skill training: a single case study

This study investigates the use of a computer training program to facilitate learning in a head-injured patient with a severe memory disturbance. The patient, DP, was taught to perform the individual steps in a morning washing and dressing routine but was unable to carry out the sequence of steps independently, in the absence of verbal prompts. A specially-constructed computer program was designed to teach these sequential links. DP was thus able to practise on the computer up to four times a day over a period of 11 weeks. Under these circumstances, the patient made rapid progress in learning the sequence of his morning routine which was shown to generalize into the functional setting. By this method DP achieved 58% success. Other memory training procedures were then instigated to fill the remaining gaps in DP's learning, thereby promoting further independence in his daily washing and dressing routine.

Intranasal oxytocin in obsessive-compulsive disorder

A 55-year patient with obsessive-compulsive disorder showed clear improvement during 4 weeks of treatment with intranasal oxytocin compared to 4 weeks of intranasal placebo. This improvement was concurrent with the development of severe memory disturbances, supporting the amnestic properties of the peptide. However, the patient also developed psychotic symptoms and a marked decrease in plasma sodium and osmolality, which may have masked the obsessive symptomatology. This case highlights the need for careful monitoring in long-term oxytocin therapy.

Thalamic mediodorsal nucleus and memory: A critical evaluation of studies in animals and man

Following a general description of the anatomical organization of the thalamic mediodorsal nucleus (MD) of animals and man, the involvement of this nucleus in the processing of memory related information has been evaluated by reviewing stimulation, electrophysiological, and lesion studies in animals, and by reviewing research on induced lesions, degenerative changes and vascular damage of MD in humans. Neither the results from animal experiments nor those from studies on humans provide clear-cut evidence for a specific, memory related role of MD. However, the findings here presented do support the theory that MD is one of several, possible memory related relay stations. While therapeutically induced and circumscribed lesions of MD rarely result in long-lasting memory deficits, pathological processes in MD are more likely to be followed by severe memory disturbances if one or more particular structures in addition to MD are included in the lesioned regions. Consequently, it is emphasized that only the disruption of more than one site along memory related pathways will result in severe and enduring memory deficits. To account for apparent inter-species differences in the involvement of MD in memory related processes, it has been argued that MD and its principal cortical target region might basically be involved in arousal and emotional processes, but that for primates and especially for man the phylogenetically young parvocellular sector of MD and its cortical projection region, the dorsolateral prefrontal cortex, are furthermore involved in memory functions, which are modulated by emotional factors via the rest of MD and the prefrontal cortex.