Clinical criteria for a limbic-predominant amnestic neurodegenerative syndrome.

Predominant limbic degeneration has been associated with various underlying aetiologies and an older age, predominant impairment of episodic memory and slow clinical progression. However, the neurological syndrome associated with predominant limbic degeneration is not defined. This endeavour is critical to distinguish such a syndrome from those originating from neocortical degeneration, which may differ in underlying aetiology, disease course and therapeutic needs. We propose a set of clinical criteria for a limbic-predominant amnestic neurodegenerative syndrome that is highly associated with limbic-predominant age-related TDP-43 encephalopathy but also other pathologic entities. The criteria incorporate core, standard and advanced features, including older age at evaluation, mild clinical syndrome, disproportionate hippocampal atrophy, impaired semantic memory, limbic hypometabolism, absence of neocortical degeneration and low likelihood of neocortical tau, with degrees of certainty (highest, high, moderate and low). We operationalized this set of criteria using clinical, imaging and biomarker data to validate its associations with clinical and pathologic outcomes. We screened autopsied patients from Mayo Clinic and Alzheimer's Disease Neuroimaging Initiative cohorts and applied the criteria to those with an antemortem predominant amnestic syndrome (Mayo, n = 165; Alzheimer's Disease Neuroimaging Initiative, n = 53) and who had Alzheimer's disease neuropathological change, limbic-predominant age-related TDP-43 encephalopathy or both pathologies at autopsy. These neuropathology-defined groups accounted for 35, 37 and 4% of cases in the Mayo cohort, respectively, and 30, 22 and 9% of cases in the Alzheimer's Disease Neuroimaging Initiative cohort, respectively. The criteria effectively categorized these cases, with Alzheimer's disease having the lowest likelihoods, limbic-predominant age-related TDP-43 encephalopathy patients having the highest likelihoods and patients with both pathologies having intermediate likelihoods. A logistic regression using the criteria features as predictors of TDP-43 achieved a balanced accuracy of 74.6% in the Mayo cohort, and out-of-sample predictions in an external cohort achieved a balanced accuracy of 73.3%. Patients with high likelihoods had a milder and slower clinical course and more severe temporo-limbic degeneration compared to those with low likelihoods. Stratifying patients with both Alzheimer's disease neuropathological change and limbic-predominant age-related TDP-43 encephalopathy from the Mayo cohort according to their likelihoods revealed that those with higher likelihoods had more temporo-limbic degeneration and a slower rate of decline and those with lower likelihoods had more lateral temporo-parietal degeneration and a faster rate of decline. The implementation of criteria for a limbic-predominant amnestic neurodegenerative syndrome has implications to disambiguate the different aetiologies of progressive amnestic presentations in older age and guide diagnosis, prognosis, treatment and clinical trials.

Is there a relationship between opioid use and transient global amnesia?

BACKGROUND AND PURPOSE: Opioid-associated amnestic syndrome (OAS) and transient global amnesia (TGA) are conditions with clinical overlap. We therefore sought to determine whether opioid use might be associated with TGA. METHODS: Data from the Massachusetts Department of Public Health Syndromic Surveillance program were queried to ascertain the frequency of opioid use among emergency department (ED) encounters for TGA compared to that for all other ED visits between January 2019 and June 2023. RESULTS: A total of 13,188,630 ED visits were identified during the study period. Of 1417 visits for TGA, one visit met the exposure definition for opioid use. There were 13,187,213 visits for other indications, 57,638 of which were considered opioid-exposed. The odds ratio for the relationship between opioid use and TGA was 0.16 (95% confidence interval 0.02, 1.14). CONCLUSION: Despite the clinical overlap between OAS and TGA, surveillance data from ED visits in Massachusetts do not suggest that opioid use is a risk factor for TGA, indicating that OAS and TGA are distinct entities.

A limbic-predominant amnestic neurodegenerative syndrome associated with TDP-43 pathology.

Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a neuropathologically-defined disease that affects 40% of persons in advanced age, but its associated neurological syndrome is not defined. LATE neuropathological changes (LATE-NC) are frequently comorbid with Alzheimer's disease neuropathologic changes (ADNC). When seen in isolation, LATE-NC have been associated with a predominantly amnestic profile and slow clinical progression. We propose a set of clinical criteria for a limbic-predominant amnestic neurodegenerative syndrome (LANS) that is highly associated with LATE-NC but also other pathologic entities. The LANS criteria incorporate core, standard and advanced features that are measurable in vivo, including older age at evaluation, mild clinical syndrome, disproportionate hippocampal atrophy, impaired semantic memory, limbic hypometabolism, absence of neocortical degenerative patterns and low likelihood of neocortical tau, with degrees of certainty (highest, high, moderate, low). We operationalized this set of criteria using clinical, imaging and biomarker data to validate its associations with clinical and pathologic outcomes. We screened autopsied patients from Mayo Clinic (n = 922) and ADNI (n = 93) cohorts and applied the LANS criteria to those with an antemortem predominant amnestic syndrome (Mayo, n = 165; ADNI, n = 53). ADNC, ADNC/LATE-NC and LATE-NC accounted for 35%, 37% and 4% of cases in the Mayo cohort, respectively, and 30%, 22%, and 9% of cases in the ADNI cohort, respectively. The LANS criteria effectively categorized these cases, with ADNC having the lowest LANS likelihoods, LATE-NC patients having the highest likelihoods, and ADNC/LATE-NC patients having intermediate likelihoods. A logistic regression model using the LANS features as predictors of LATE-NC achieved a balanced accuracy of 74.6% in the Mayo cohort, and out-of-sample predictions in the ADNI cohort achieved a balanced accuracy of 73.3%. Patients with high LANS likelihoods had a milder and slower clinical course and more severe temporo-limbic degeneration compared to those with low likelihoods. Stratifying ADNC/LATE-NC patients from the Mayo cohort according to their LANS likelihood revealed that those with higher likelihoods had more temporo-limbic degeneration and a slower rate of cognitive decline, and those with lower likelihoods had more lateral temporo-parietal degeneration and a faster rate of cognitive decline. The implementation of LANS criteria has implications to disambiguate the different driving etiologies of progressive amnestic presentations in older age and guide prognosis, treatment, and clinical trials. The development of in vivo biomarkers specific to TDP-43 pathology are needed to refine molecular associations between LANS and LATE-NC and precise antemortem diagnoses of LATE.

Case report: severe course of encephalitis of unknown origin.

The exact cause of encephalitis is still unclear in many cases, although the common etiological factors of this process are viruses such as herpes simplex virus and rabies virus, and also bacteria, fungi, parasites, several medicines and autoimmune diseases. Herein, we report a case of a 56-year-old man with a history of amnestic syndrome, impaired consciousness, somnolence throughout the day, headache, dizziness and hypertension, who was admitted to hospital with suspected neurological disease, and imaging features that were consistent with encephalitis of unknown etiology. Methods which were used to examine patient: cerebrospinal fluid testing, PCR examinations for viruses, testing of antibodies against surface antigens, magnetic resonance imaging of the head, psychiatric consultation, oncology consultation. The objective of this study is to demonstrate a case about an uncommon neurologic condition, which every clinician might meet in clinical practice. In this type of cases, the use of steroids such as dexamethasone and methylprednisolone might lead to a full recovery.

Hippocampal and Cerebellar Involvement in Opioid-Associated Amnestic Syndrome: A Unique Case Report.

We present a case of opioid-associated amnestic syndrome (OAS) in a 46-year-old female with persistent acute anterograde amnesia and biochemically confirmed with fentanyl use. The brain Magnetic Resonance Imaging (MRI) examination demonstrated symmetric restricted diffusion and T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities in the hippocampi and cerebellum. While cases of cerebellar findings in OAS are rare in the literature, this is a unique case with corresponding images that demonstrate cerebellar involvement in addition to the more common hippocampal finding.

The amnestic syndrome of posterior cerebral artery infarction.

BACKGROUND AND PURPOSE: Little is known about the character and underlying lesions of ischaemic amnesia. Episodic memory functions and brain lesions were therefore studied in 84 patients with acute ischaemic infarcts in the supply territory of the posterior cerebral artery. The aim was also to learn how the neural memory systems are organized. METHODS: Standard neuropsychological tests were used to assess verbal and figural memory. Patients were split into memory-impaired and memory-intact groups. Lesions were demarcated, normalized and anatomically labelled, using standard mapping procedures. RESULTS: Of the 84 patients more than 80% had an amnestic syndrome, mostly with combined memory impairment, less often with figural or verbal memory impairment. Amnesia in subjects with left hemispheric lesions was more frequent and more severe, with significantly lower scores on the verbal memory test. Normal performance or figural amnesia were prevalent after right hemispheric lesions. However, no amnesia subtype was strictly tied to left- or right-sided brain damage. Hippocampal and thalamic lesions were common, but 30% of lesions were extrahippocampal located in the ventral occipito-temporal cortex and long occipital white matter tracts. Most amnestic patients lacked awareness for their memory impairment. CONCLUSIONS: Memory impairment is a key clinical manifestation of acute posterior cerebral artery stroke. Amnesia is more frequent and more severe after left stroke, suggesting a left hemisphere dominance of the two memory systems. Domain specific memory appears not to be strictly lateralized, since deficits in verbal and figural memory were found after lesions of both sides. Extrahippocampal lesions may also cause memory impairment.

[Memory Loss - a Case of Sudden Amnesia]. / Herr B. kann sich nicht mehr erinnern ­ wenn das Gedächtnis gelöscht ist.

Memory Loss - a Case of Sudden Amnesia Abstract. Transient global amnesia (TGA) is a clinical diagnosis with typical signs of an anterograde and retrograde amnesia. The underlying mechanisms are yet unknown, different hypotheses are being discussed. Ultimately there is a temporary dysfunction of the hippocampi. Consistent with this, transient uni- or bilateral punctiform hyperintense lesions may be found on DWI-MRI sequences, usually without correlation on FLAIR-weighthed MR-images. Symptoms usually resolve within twenty-four hours. There is no need for a specific therapy. A prophylactic therapy, such as antithrombotic treatment, is not indicated. The prognosis is usually good, the risk of a recurrence is about 18%.

Opioid-Associated Amnestic Syndrome.

Opioid-associated amnestic syndrome (OAS) is a relatively new condition that is associated with opioid abuse and has increased in prevalence since the notable rise in opioid-related deaths and opioid-related hospitalizations of the opioid crisis. Patients often present with acute anterograde amnesia and current opioid abuse, most commonly fentanyl. OAS is frequently diagnosed when other potentially infectious or metabolic conditions such as encephalitis and seizures are ruled out, as these conditions can also present similarly to OAS. This case highlights the signs, symptoms, and hallmark characteristics of OAS, including bilateral hippocampal edema and anterograde amnesia.

Opioid-Associated Amnestic Syndrome.

A 31-year-old male with a history significant for obesity, attention deficit hyperactivity disorder, methamphetamine use, and IV drug use was evaluated for unexplained global amnesia greater than 24 h. The patient had been in recovery for opioid use disorder for about a year, but he relapsed on IV fentanyl in the week prior to presentation. On exam, he was alert and fully oriented but had no spontaneous recall of three objects after five minutes. General medical and neurological examinations were otherwise unrevealing. Urine fentanyl and norfentanyl were positive. CT and MRI imaging demonstrated isolated bilateral hippocampal injury. Given the totality of his presentation and the contributing variables, his medical team considered this to be a case of the newly characterized opioid-associated amnestic syndrome (OAS). This case is significant because of the relative absence of potentially confounding variables on presentation, including antecedent cardiorespiratory failure. Further reporting of these cases may have implications for understanding opioid toxicity and clarifying the functional role of the hippocampus.

Opioid-associated amnestic syndrome: Description of the syndrome and validation of a proposed definition.

OBJECTIVE: An opioid-associated amnestic syndrome (OAS) characterized by acute onset memory loss and bilateral hippocampal signal abnormalities on brain imaging in the setting of a history of opioid use, most notably fentanyl, has been reported. To date, however, there is no case definition to assist neurologists and other clinicians in identifying this syndrome. A multi-disciplinary collaboration of physicians, including neurologists, propose diagnostic criteria for OAS using cases that have been published in the medical literature or presented at conferences. METHODS: Cases were classified as confirmed, probable, or possible based on brain imaging findings and history or analytical testing supporting opioid use. Published articles and presentations were identified by discussion with public health authorities and a systematic search of PubMed. Included were articles, abstracts or posters through November 2019 that presented case reports or case series of a new-onset amnestic syndrome associated with bilateral hippocampal injury on imaging and/or prior opioid or other substance use. The percentages of cases that would meet confirmed, probable, or possible criteria were calculated. RESULTS: Twenty-three publications from all sources met criteria for inclusion, accounting for 40 unique cases. Based on the case definition of OAS, 50% (20/40) were confirmed, 25% (10/40) were probable and 25% (10/40) were possible. CONCLUSION: The development of a validated, formal case definition for OAS can assist neurologists and other clinicians in evaluating patients with amnesia and a history of opioid use.

Korsakoff syndrome from retrochiasmatic suprasellar lesions: rapid reversal after relief of cerebral compression in 4 cases.

Korsakoff syndrome is a chronic memory disorder caused by a severe deficiency of thiamine that is most commonly observed in alcoholics. However, some have proposed that focal structural lesions disrupting memory circuits-in particular, the mammillary bodies, the mammillothalamic tract, and the anterior thalamus-can give rise to this amnestic syndrome. Here, the authors present 4 patients with reversible Korsakoff syndromes caused by suprasellar retrochiasmatic lesions compressing the mammillary bodies and adjacent caudal hypothalamic structures. Three of the patients were found to have large pituitary macroadenomas in their workup for memory deficiency and cognitive decline with minimal visual symptoms. These tumors extended superiorly into the suprasellar region in a retrochiasmatic position and caused significant mass effect in the bilateral mammillary bodies in the base of the brain. These 3 patients had complete and rapid resolution of amnestic problems shortly after initiation of treatment, consisting of resection in 1 case of nonfunctioning pituitary adenoma or cabergoline therapy in 2 cases of prolactinoma. The fourth patient presented with bizarre and hostile behavior along with significant memory deficits and was found to have a large cystic craniopharyngioma filling the third ventricle and compressing the midline diencephalic structures. This patient underwent cyst fenestration and tumor debulking, with a rapid improvement in his mental status. The rapid and dramatic memory improvement observed in all of these cases is probably due to a reduction in the pressure imposed by the lesions on structures contiguous to the third ventricle, rather than a direct destructive effect of the tumor, and highlights the essential role of the caudal diencephalic structures-mainly the mammillary bodies-in memory function. In summary, large pituitary lesions with suprasellar retrochiasmatic extension and third ventricular craniopharyngiomas can cause severe Korsakoff-like amnestic syndromes, probably because of bilateral pressure on or damage to mammillary bodies, anterior thalamic nuclei, or their major connections. Neuropsychiatric symptoms may rapidly and completely reverse shortly after initiation of therapy via surgical decompression of tumors or pharmacological treatment of prolactinomas. Early identification of these lesions with timely treatment can lead to a favorable prognosis for this severe neuropsychiatric disorder.

A case of reversible anti-NMDA-receptor encephalitis: neuropsychological and neuroradiological features.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune encephalitis mainly affecting young women. We report a case of a mild paraneoplastic anti-NMDAR encephalitis in a 31-year-old female with an ovarian immature teratoma. The patient exhibited a severe short-term episodic memory impairment and psychiatric symptoms. A detailed diagnostic work-up including complete clinical and laboratory examinations, neuropsychological assessments, and neuroradiological investigations has been done at the onset and during follow-up. The amnestic syndrome and MRI medial-temporal abnormalities reversed after medical and surgical treatment. The present report indicates that the disease can be rapidly reversible if promptly diagnosed and treated. While the disease has already been described elsewhere, the course of neurospychological deficits in adults is not as much known. Usually, when the diagnosis of anti-NMDAR encephalitis is made, the severity of the disease makes the assessment of the neuropsycological profile particulary challenging. The present report is of interest because it describes the complete neuropsychological profile of a mild form of anti-NMDAR encephalitis.

Evidence for a Common Founder and Clinical Characteristics of Japanese Families with the MAPT R406W Mutation.

BACKGROUND/AIM: Mutations in MAPT cause frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). Patients with the MAPT R406W mutation were reported to show phenotypic heterogeneity in different ethnic backgrounds. We here report the clinical and genetic characteristics of Japanese families with the R406W mutation. METHODS: We examined the clinical and neuroimaging features of 6 patients from three families with the R406W mutation. We determined the genotypes of intragenic MAPT single-nucleotide polymorphisms (SNPs) and the flanking microsatellite markers to search for a common founder. RESULTS: The initial symptom was memory loss with the average age at onset being 54 years. Anterograde amnesia with episodic memory impairment was the predominant phenotype. Behavioral and personality changes or parkinsonism is not a prominent feature. A brain MRI study revealed marked atrophy of the medial temporal lobe. Genetic analysis of SNPs and microsatellite markers revealed that the affected members of the three families share common genotypes. CONCLUSION: The findings of the affected members in this study, which corroborate previously reported findings of European families, suggest that the R406W mutation may represent a phenotype of predominant anterograde amnesia in FTLD-17. Our genetic data suggest that a founder effect may account for some families with the R406W mutation.

When Alcoholism Affects Memory Functions: MRI of the Brain.

The development of modern imaging techniques makes it possible to examine directly the relationship between brain abnormalities and memory impairment. Alcoholic amnesics may perform normally on certain tests (priming tasks) that require implicit (unconscious) memory, even though they may not be able consciously to recall the memory. Researchers have therefore postulated the existence of multiple memory mechanisms. Magnetic resonance imaging (MRI) observations suggest that independent memory mechanisms are not necessary to explain the dissociation between explicit and implicit memory. Alcoholic amnesics appear to suffer from damage to structures in two areas of the brain, affecting two separate processing components that are both required in most priming tasks: a stimulus processing component and a memory processing component.