Bilateral Hippocampal Atrophy Research Articles

A 21-Years-Old Man with Mesial Temporal Lobe Epilepsy and Dystonia: A Rare Case Report

Background: Mesial temporal lobe epilepsy (MTLE) with dystonia is a rare case. Seizures and movement disorders have almost the same phenomenology, so it is often difficult to distinguish them. In this study, we report a unique case of MTLE and co-occurring dystonia. Case: A 21 years old male with complaints of seizures since 4 years ago. Seizures of one body jerking and drooling with a duration of less than 5 minutes. Prior to the seizure the patient was nauseous then vomited and followed by an empty mind, after the seizure the patient was confused. The patient also complained of unconscious movements in his right hand since 8 years ago. The movements disappeared when the patient slept. Physical examination revealed dystonic movement with a sensory trick on the right hand. Magnetic resonance imaging (MRI) of the brain with contrast showed bilateral hippocampal atrophy accompanied by left hippocampal sclerosis. Blood laboratory results, electroencephalography, and neurobehavior examination were within normal limits.. Discussion: MTLE can be caused by mutations in SCN1A, VPS13A, C90RF72, or TDP 43. Dystonia can be caused by mutations in SCN1A, TUBB4A, TOR1A, THAP1, or GNAL. SCN1A causes an increase in sodium influx, causing depolarization which causes clinical manifestations in the form of seizures and dystonia. For some disorders, although genetic causes have been identified, the molecular pathophysiology remains largely unknown, requiring further research. Conclusion: For some disorders, although genetic causes have been identified, the molecular pathophysiology remains largely unknown, requiring further research.

Mapping hippocampal and thalamic atrophy in epilepsy: A 7-T magnetic resonance imaging study.

Epilepsy patients are often grouped together by clinical variables. Quantitative neuroimaging metrics can provide a data-driven alternative for grouping of patients. In this work, we leverage ultra-high-field 7-T structural magnetic resonance imaging (MRI) to characterize volumetric atrophy patterns across hippocampal subfields and thalamic nuclei in drug-resistant focal epilepsy. Forty-two drug-resistant epilepsy patients and 13 controls with 7-T structural neuroimaging were included in this study. We measured hippocampal subfield and thalamic nuclei volumetry, and applied an unsupervised machine learning algorithm, Latent Dirichlet Allocation (LDA), to estimate atrophy patterns across the hippocampal subfields and thalamic nuclei of patients. We studied the association between predefined clinical groups and the estimated atrophy patterns. Additionally, we used hierarchical clustering on the LDA factors to group patients in a data-driven approach. In patients with mesial temporal sclerosis (MTS), we found a significant decrease in volume across all ipsilateral hippocampal subfields (false discovery rate-corrected p [pFDR] < .01) as well as in some ipsilateral (pFDR < .05) and contralateral (pFDR < .01) thalamic nuclei. In left temporal lobe epilepsy (L-TLE) we saw ipsilateral hippocampal and some bilateral thalamic atrophy (pFDR < .05), whereas in right temporal lobe epilepsy (R-TLE) extensive bilateral hippocampal and thalamic atrophy was observed (pFDR < .05). Atrophy factors demonstrated that our MTS cohort had two atrophy phenotypes: one that affected the ipsilateral hippocampus and one that affected the ipsilateral hippocampus and bilateral anterior thalamus. Atrophy factors demonstrated posterior thalamic atrophy in R-TLE, whereas an anterior thalamic atrophy pattern was more common in L-TLE. Finally, hierarchical clustering of atrophy patterns recapitulated clusters with homogeneous clinical properties. Leveraging 7-T MRI, we demonstrate widespread hippocampal and thalamic atrophy in epilepsy. Through unsupervised machine learning, we demonstrate patterns of volumetric atrophy that vary depending on disease subtype. Incorporating these atrophy patterns into clinical practice could help better stratify patients to surgical treatments and specific device implantation strategies.

Exploring graded profiles of hippocampal atrophy along the anterior-posterior axis in semantic dementia and Alzheimer’s disease

Mounting evidence indicates marked hippocampal degeneration in semantic dementia (SD) however, the spatial distribution of hippocampal atrophy profiles in this syndrome remains unclear. Using a recently developed parcellation approach, we extracted hippocampal volumes from four distinct subregions running from anterior to posterior along the longitudinal axis (anterior, intermediate rostral, intermediate caudal, and posterior). Volumetric differences in hippocampal subregions were compared between 21 SD, 24 matched Alzheimer’s disease (AD), and 27 healthy older Control participants. Despite comparable overall hippocampal volume loss, SD and AD groups diverged in terms of the magnitude of atrophy along the anterior-posterior axis of the hippocampus. Global hippocampal atrophy was observed in AD, with no discernible gradation or lateralisation. In contrast, SD patients displayed graded bilateral hippocampal atrophy, most pronounced on the left-hand side, and concentrated in anterior relative to posterior subregions. Finally, we found preliminary evidence that disease-specific vulnerability along the anterior-posterior axis of the hippocampus was associated with canonical clinical features of these syndromes.

57 Clinical Utility of Neuropsychological Evaluation in the Differential Diagnosis Between Late-Onset Primary Progressive Aphasia Semantic Variant (PPA-SV) Versus Limbic Predominant Age-Related TDP-43 Encephalopathy (LATE): A Case Report

Objective:Primary progressive aphasia semantic variant (PPA-SV) is an atypical dementia subtype on the frontotemporal dementia (FTD) spectrum. PPA-SV is clinically defined by naming and semantic deficits, with progressive language decline that generalizes to other domains over time. Typically, it presents as an early-onset dementia with TDP-43 pathology, but 33-46% of PPA-SV cases display initial onset after age 65 with potentially different clinical features. Limbic Predominant Age-Related TDP-43 Encephalopathy (LATE), a more recently discovered neurodegenerative entity, is defined by an older age of onset, hippocampal sclerosis/atrophy, and TDP-43 pathology with a gradually progressive amnestic profile that expands to other cognitive deficits over time. The authors present a case report with overlapping features and suspected TDP-43 neuropathology ante-mortem for two reasons: first, to highlight the need for clinical criteria to formally diagnose LATE, and second, to address a gap in the literature on the possible clinical differences of late-onset PPA-SV.Participants and Methods:The authors present a case of a 78-year-old Indian bilingual man (English dominant) with 18 years of education, noncontributory medical history, and gradually progressive cognitive complaints reported over the past few years who was seen for outpatient neuropsychological evaluation. Prior workup was notable for negative amyloid PET scan, negative p-tau 217 blood test, and abnormal brain MRI revealing marked bilateral hippocampal atrophy with ex vacuo ventriculomegaly and minimal cerebrovascular disease. He scored 23/30 on prior MMSE, was diagnosed with amnestic MCI, prescribed Namenda and Exelon, and complained of minor memory and word-finding difficulties with reportedly intact IADLs and no signs of NPH.Results:Neuropsychological testing revealed a profound dysnomia (RBANS Naming raw score = 1/10), and he provided 0 words on two semantic fluency tasks but 15 words on letter fluency. Receptive vocabulary score was also impaired (PPVT-4, &lt;1st %). Memory performance also demonstrated rapid forgetting of information (RBANS List Recall raw = 0/10, Story Recall raw = 0/12) with no benefit to recognition cues (RBANS List Recognition raw = 12/20), but slightly better visual memory recall, albeit still impaired (RBANS Figure Recall raw = 4/20). Grooved pegboard scores were significantly worse with right-hand than left-hand. Irregular word reading (NAART = 16th %ile) was significantly below expectations and thought to reflect more of a surface dyslexia rather than a cultural confounder given that he has lived in the US for over 50 years and his occupational and educational history was completed in English.Conclusions:Results support the clinical utility of neuropsychological evaluation in the differential diagnosis to support a predominant clinical syndrome of PPA-SV despite overlapping features with LATE and suspected TDP-43 pathology. This case report highlights the diagnostic issue with the lack of literature describing the typical clinical progression or suggested diagnostic criteria of LATE. These findings also indicate that late-onset PPA-SV may include greater memory deficits earlier in the course, but this may also be a clinical masquerade that is more reflective of the extent of language deficits. Further research on late-onset manifestations of PPA-SV and LATE consensus clinical guidelines is advised.

MR-based spatiotemporal anisotropic atrophy evaluation of hippocampus in Alzheimer's disease progression by multiscale skeletal representation.

Increasing evidence has shown a higher sensitivity of Alzheimer's disease (AD) progression by local hippocampal atrophy rather than the whole volume. However, existing morphological methods based on subfield-volume or surface in imaging studies are not capable to describe the comprehensive process of hippocampal atrophy as sensitive as histological findings. To map histological distinctive measurements onto medical magnetic resonance (MR) images, we propose a multiscale skeletal representation (m-s-rep) to quantify focal hippocampal atrophy during AD progression in longitudinal cohorts from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The m-s-rep captures large-to-small-scale hippocampal morphology by spoke interpolation over label projection on skeletal models. To enhance morphological correspondence within subjects, we align the longitudinal m-s-reps by surface-based transformations from baseline to subsequent timepoints. Cross-sectional and longitudinal measurements derived from m-s-rep are statistically analyzed to comprehensively evaluate the bilateral hippocampal atrophy. Our findings reveal that during the early AD progression, atrophy primarily affects the lateral-medial extent of the hippocampus, with a difference of 1.8 mm in lateral-medial width in 2 years preceding conversion (p < .001), and the medial head exhibits a maximum difference of 3.05%/year in local atrophy rate (p = .011) compared to controls. Moreover, progressive mild cognitive impairment (pMCI) exhibits more severe and widespread atrophy in the head and body compared to stable mild cognitive impairment (sMCI), with a maximum difference of 1.21 mm in thickness in the medial head 1 year preceding conversion (p = .012). In summary, our proposed method can quantitatively measure the hippocampal morphological changes on 3T MR images, potentially assisting the pre-diagnosis and prognosis of AD.

A case of early‐onset familial Alzheimer’s disease caused by PSEN1 gene Y115C mutation in a Chinese pedigree

AbstractBackgroundAlzheimer’s disease is the most common cause of dementia, with approximately 0.9% associated with known genetic mutations. Presenilin 1(PSEN1) gene is one of the most common genes associated with early‐onset familial Alzheimer’s disease (EOFAD). We reported a case of EOFAD with Y115C mutation of PSEN1 gene which was the first report in China.MethodAn early‐onset Alzheimer’s patient from Beijing Tiantan Hospital, Capital Medical University and her family were enrolled as the research object. The clinical and imaging data of the proband were collected. The genomic DNA from peripheral venous blood of the proband was screened.ResultThere were 6 members with memory and working competence loss in this pedigree. The proband, whose age of onset was 42 years old, was manifested as memory loss for more than 1year. She became apathetic, lazy in housework but without abnormal mood and behavior. She was healthy in the past, denied smoking and drinking history. Her grandmother, mother, aunt, uncle and brother all showed memory loss. Her brother is now unable to complete the driver’s work. The physical examination showed poor memory, calculation, orientation, executive functions, slow reaction and poor comprehension. The MMSE score was 11, MoCA‐Beijing score was 5, ADL‐20 score was 28, HAMD score was 2, HAMA score was 1 and PSQI score was 5. Head MRI of the proband showed whole cerebral cortical atrophy and bilateral hippocampal atrophy, obviously on the left side. The arterial spin labeling finding showed significantly reduced blood perfusion in the left cortex and hippocampus. A c.344A &gt; G (p. Tyr115Cys) pathogenic mutation in the exon 5 of PSEN1 gene was found, proving the diagnosis.ConclusionWe reported this EOFAD case caused by Y115C mutation of PSEN1 gene in a Chinese family to enrich the genetic and clinical phenotypic characteristics in China. Gene detection plays an important role in the diagnosis of the early‐onset Alzheimer’s disease.

The Presence or Absence of Hippocampal Atrophy Differently Disrupts Graph Theory Properties of Cerebral Functional Connectivity in Temporal Lobe Epilepsy. (S30.004)

<h3>Objective:</h3> To investigate brain connectivity and network properties with graph theory methods in TLE patients according to the presence or absence of HA. <h3>Background:</h3> Although temporal lobe epilepsy (TLE) with unilateral hippocampal atrophy (HA) has been extensively investigated, the impact of bilateral HA and the absence of HA on brain connectivity and networks’ efficiency remains unknown. <h3>Design/Methods:</h3> We analyzed 216 3T-MRI resting-state images of TLE patients (median age: 48 years; 122 women): 92 LEFT-HA, 70 RIGHT-HA, 25 BILATERAL-HA, 29 NEGATIVE-TLE, and 216 healthy controls. We used the CONN connectivity_toolbox/MATLAB2019 to extract graph theory measures (global efficiency (Global-eff), average path length (PATH), degree/cost (DEGREE), betweenness centrality (BC), local efficiency (Local-eff), and clustering coefficient (CC). We considered a cost of 0.15 (including only the 15% more statistically significant results) and reported p-values&lt;0.05. <h3>Results:</h3> The LEFT-HA and RIGHT-HA presented a trend to higher measures of global connectivity (Global-Con), local connectivity (Local-Con), and centrality in the brain (higher Global-eff, DEGREE, BC, Local-eff, CC, and lower PATH) and a trend to lower Global-Con, Local-Con, and centrality in the cerebellum. The LEFT-HA and RIGHT-HA presented higher DEGREE in the ipsilateral hippocampus and higher Local-eff /CC in the contralateral hippocampus. The NEGATIVE-TLE group showed a trend to lower Global-eff and higher average PATH, DEGREE and CC in the brain. The BILATERAL-HA presented a trend to higher Local-eff /CC in the brain. <h3>Conclusions:</h3> Overall, there was a trend for higher local connectivity to the detriment of the Global-eff. Our data indicate more severe alterations in the unilateral groups, as the presence of unilateral HA disturbs hemispheric connectivity, which may disrupt global connections. While the unilateral groups showed higher connectivity levels in the brain (with higher ipsilateral hippocampal Global-Con and probable compensatory higher contralateral hippocampal Local-Con), the NEGATIVE-TLE presented concordantly higher Local-Con and lower Global-Con in the brain. <b>Disclosure:</b> Lucas Silva has nothing to disclose. Dr. Karmann Aventurato has received research support from Coordenadoria de Aperfeiçoamento de Pessoal de Ensino Superior (CAPES). Raphael Casseb has nothing to disclose. The institution of Brunno de Campos has received research support from São Paulo Research Fundation. Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Pharma. Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB Biopharma. Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for United Medical – Brazil. Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Zodiac Pharma . Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eurofarma – Brazil . Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Epilepsia. Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers in Neurology - Epilepsy. The institution of Dr. Cendes has received research support from São Paulo Research Foundation - FAPESP. The institution of Dr. Cendes has received research support from Conselho Nacional de Desenvolvimento Científico e Tecnológico - Brazil . The institution of Dr. Cendes has received research support from NIH. Clarissa Yasuda has nothing to disclose.

Hemodynamics of ictal hyperperfusion in an epileptic patient with dual pathology revealed by arterial spin labeling perfusion image with triple postlabeling delays

The hemodynamics of ictal hyperperfusion in dual pathology was evaluated using arterial spin labeling perfusion images (ASL) with triple postlabeling delays (PLDs). A 62-year-old man with epileptogenic right parietal hematoma cavity and bilateral hippocampal atrophy, particularly on the right, underwent ASL examination during subtle non-convulsive status epilepticus immediately after focal-to-bilateral tonic-clonic seizures. ASL at PLD of 1.5 s showed increased signals in the gray matter of both hemispheres, in addition to the peri-cavitary cortex. At PLD of 1.75 s, these signals were mostly washed out, and there was a marked increase in signals localized to bilateral hippocampal heads. The hippocampal signals were also mostly washed out at PLD of 2.0 s. These findings indicate a close relationship between activities originating from the peri-cavitary cortex and the hippocampus in this case. In terms of the mechanism of hippocampal atrophy, the oxygen supply required for large epileptic activities could not be met.

Two Cases of Isolated Neurofilament Heavy Chain Antibody Syndrome

Objective Novel clinical and laboratory findings in anti-neurofilament heavy chain encephalitis Background Antibodies to mature components of neuronal intermediate filament (NIF) have been implicated in several neurological disorders, including multiple sclerosis, amyotrophic lateral sclerosis, and more recently, various autoimmune encephalitides. The components include a-internexin, light chain and heavy chain. In the largest case series of anti-NIF syndromes (McKeon et al, 2021), patients' cell-based assays revealed antibodies to one, two or all three components. Heavy chain antibodies (anti-NfH) were present in most, including three out of four patients with encephalopathy and cerebellar involvement. One was due to a paraneoplastic phenomenon. Anti-NfH was also elevated in two cases of encephalopathy with spasticity. It was the lone autoantibody in one of the six aforementioned cases. Design/Methods N/A. Results Case 1: 37-year old female with a history of ovarian carcinoma, treated in 2016. Cognitive impairment started in fall 2019, with significant worsening to the point of catatonia and coma in October 2020. Though encephalopathy improved, severe ataxia and nystagmus persisted. Two MRI brain studies and an EEG were unremarkable, and no radiological evidence of cancer recurrence. Oligoclonal bands (in both CSF and serum) and serum anti-NfH were elevated. Case 2: 59 year-old female with gradual cognitive decline since March 2018, followed by rapid cognitive deterioration in Oct 2020. There was limb weakness, severe rigidity, clonus and a witnessed seizure. EEG showed intermittent rhythmic delta activity. MRI brain indicated severe bilateral hippocampal atrophy. CSF Protein and CSF anti-NfH were elevated. Conclusions This case series contains the first reported paraneoplastic encephalopathy with cerebellar involvement from isolated anti-NfH. Also presented is the first reported case of PERMS from any NIF antibody. Further research is needed on quantitative and qualitative factors of anti-NIF syndromes. Specifically, the clinical relevance of the number of antibodies, and associations between phenotype and specific antibody combination.

Clinical characterization of Colombian families with frontotemporal dementia due to the MAPT P397S mutation

AbstractBackgroundMutations in the microtubule associated protein tau (MAPT) gene located in chromosome 17 have been associated with frontotemporal dementia (FTD). The novel mutation Pro397Ser, with an autosomal dominant inheritance pattern has been recently reported in Spain (Borrego‐Écija et al., 2019). The Group of Neuroscience of the University of Antioquia in Colombia has identified several families with mutations leading to FTD. Here we present the initial clinical characterization of individuals carrying the MAPT P397S mutation.MethodA total of 30 family members were included (15 carriers and 15 non‐carriers, 18 – 76 years old). All participants underwent a comprehensive neurological and neuropsychological evaluation. They also completed self‐reported measures of depression and behavioral symptoms. Mann‐Whitney tests were used to test between‐group differences in cognitive measures. Spearman correlations were used to examine associations among outcome measures and age.ResultMean age was 48.7 years (SD 16.4), and mean education was 10.7 years (SD=4.56). Six carriers were classified as cognitively impaired (MCI= 3, moderate/severe dementia= 3). Mean age of clinical was 50 years. Initial symptomatology was predominantly behavioral (disinhibition, aggressiveness, loss of empathy, compulsiveness, dietary changes) followed by loss of executive function, memory, language skills and decline in ADLs in affected individuals. Structural MRIs showed frontotemporal lobar degeneration in all impaired carriers, and additional bilateral hippocampal atrophy with left predominance in two of them. The cognitive profile of carriers was characterized by lower scores in measures of executive function, semantic processing and short‐term memory loss. Cognitively unimpaired carriers had statistically significant worse performance on the INECO Battery, a measure of executive function, compared to non‐carriers, several years prior to their clinical onset.ConclusionInitial findings showed that the clinical profile of Colombian families with the MAPT‐P397S novel mutation is characterized by executive dysfunction, behavioral changes, semantic language alterations and memory loss. Findings suggest that the INECO Battery may be a sensitive tool to detect subtle changes in executive function in cognitively unimpaired carriers of this mutation. Longitudinal follow‐up of these individuals will be important to better characterize the disease progression from preclinical to clinical stages. Future studies should consider adding neuroimaging and other biomarker measures.

Title: Poor Long-Term Outcomes of Patients with Human Herpesvirus 6 Encephalitis

Background:Human herpesviruses 6 (HHV-6) A and B cause encephalitis in patients with hematologic malignancies especially those undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Data on the long-term outcomes of patients with HHV-6 encephalitis is limited.Methods:To assess the clinical and diagnostic characteristics, and outcomes of patients with HHV-6 encephalitis, we performed a retrospective review of all patients with positive HHV-6 in plasma or CSF between Nov 2011 and Jun 2017. Cases were categorized based on pre-defined criteria for possible, probable and definite HHV-6 encephalitis.Results:Ten patients with leukemia (n=5), lymphoma (n=2), and other hematologic cancers (n=3) met the criteria for definite (n=8), probable (n=1) and possible (n=1) HHV-6 encephalitis (Table 1). All except one were allogeneic HSCT recipients (three umbilical cord and six matched unrelated donors). Among 9 cases, the median time to onset of illness was early at 23 days (IQR: 20.5-29.5) after transplantation. The clinical symptoms were confusion (80%), retrograde amnesia (60%), fever (50%), rash (50%) and seizures (20%). Before or at the time of illness, patients had GVHD (55%), pre-engraftment syndrome (44%) and CMV (22%). CSF showed mild pleocytosis (WBC 5-22; n=6) and elevated protein (n=8). Plasma HHV-6 PCR was negative in 2 cases, while brain MRI was normal in one definitive case. The most common MRI abnormality was increased T2 signal in the bilateral hippocampal (40%) and mesial temporal lobes (50%). All patients received intravenous ganciclovir for a median duration of 27 days (range: 10-48). Follow-up MRI at 4-40 weeks in 6 patients showed moderate to severe bilateral hippocampal atrophy (50%) or no interval improvement (33%). Five patients died; none were due to HHV-6 encephalitis.One patient developed possible HHV-6 encephalitis with retinitis at post-transplant day +429; despite clinical improvement, the HHV-6 load remained at >2x106 copies/ml suggesting this case as reactivated chromosomally integrated-HHV-6.Conclusions:HHV-6 infection among patients with hematologic malignancies and transplantation is associated with significant long-term morbidity and all-cause mortality. A negative plasma HHV-6 PCR does not rule out the diagnosis. Despite prolonged treatment, persistent neurologic deficits associated with moderate to severe bilateral hippocampal atrophy are characteristic long-term findings. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Cognitive consequences of COVID-19 in older adults with cognitive impairment

IntroductionCoronavirus disease 2019 (COVID-19) is due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with significant morbidity and mortality that is well documented. This includes significant central nervous system (CNS) involvement that ranges from acute delirium to meningoencephalitis. While acute symptoms and manifestations have been noted, long-term neuropsychiatric and cognitive outcomes remain unclear in convalescent COVID-19 patients. Characterizing the convalescence is particularly important since 80% recover, yet the relationship between exacerbated cognitive dysfunction and COVID-19 remains unclear. We describe 3 adults above age 65 who reported worsening cognitive symptoms in the convalescent stage of COVID-19.MethodsThree adults above the age of 65 who noted worsening cognitive difficulties after SARS-CoV-2 infection and COVID-19 were evaluated in the Memory Clinic of the Duke Neurological Disorders Clinic. Electronic medical records were retrospectively reviewed. Exam included a comprehensive neurological evaluation, formal neuropsychological evaluation, and neuroimaging. Prior history was collected for comparison with their current clinical evaluation profile data.ResultsPatient 1 is a 69 year old diabetic, hypertensive male with a history of depression and a first-order relative and a maternal aunt with late-onset Alzheimer's disease dementia who presented for evaluation of memory loss first noted about one year prior but had significantly worsened in the five months since his recovery from COVID-19. He had documented antibodies to SARS-CoV-2. The patient reported forgetting when he had eaten and now evinces navigation issues even when driving on familiar roads. Head CT without contrast obtained before COVID-19 infection showed mild bilateral hippocampal atrophy. He scored 4/8 on the AD8 Dementia Screening and 20/30 on the Montreal Cognitive Assessment (MoCA). PHQ9 was 10, GAD7 was 0, and NPI was 1. Formal neuropsychological evaluation data were collected. A diagnosis of late-onset Alzheimer's disease without behavioral disturbance was made during his clinic visit. Donezepil was started. Other comorbidities included vitamin B12 deficiency, atrial fibrillation, congestive heart failure, chronic obstructive pulmonary disease, obstructive sleep apnea, and morbid obesity.Patient 2 is a 68 year old male with a history of anxiety, depression, and attention deficit disorder who presented for evaluation of poor memory, inability to “visually map,” and daily “senior moments” as well as a prolonged period of confusion while driving four months after recovering from COVID-19. He had documented antibodies to SARS-CoV-2. He had transient memory problems two years ago that improved after changing his bupropion dosage. He also takes fluoxetine. He now regularly misplaces objects and often stops a task midway through, thinking that he completed it. His GDS score was 5. Head CT was unremarkable. MRI of the brain demonstrated mild hippocampal and biparietal lobe atrophy as well as mild cerebral white matter disease. He scored 7/8 on the AD8 Dementia Screening and 27/30 on the MoCA. A diagnosis of dementia with behavioral disturbance was made. PHQ9 was 9, GAD7 was 6, and NPI was 7. B12 was normal. There is no family history of cognitive impairment.Patient 3 is a 76-year-old female with a history of bipolar 1, diabetes, hypothyroidism, hyperlipidemia who presented for evaluation of memory loss that started 6 months ago but worsened since she had recovered from COVID-19 diagnosed about 8 weeks earlier. After testing positive, she was hospitalized for 3 weeks due to acute encephalopathy attributed to lithium toxicity. She was also taking trazodone. Her GDS score was 7. She scored 8/8 on the AD8 Dementia Screening. MoCA could not be completed. PHQ9 was 3, GAD7 was 9, and NPI was 19. Formal neuropsychological evaluation data were collected. Head CT without contrast three weeks after COVID-19 diagnosis showed calcification in the right basal ganglia, a mild hypodense signal periventricularly, and gray-white differentiation. Brain MRI without contrast showed subtle hippocampal and perisylvian atrophy on T1, mild to moderate parietal lobe atrophy bilaterally, and mild to moderate periventricular leukoaraiosis/white matter hyperintensities on FLAIR sequence. A diagnosis of dementia without behavioral disturbance was made. There is a family history of bipolar disorder in siblings and cognitive impairment in her father but no specific diagnosis of dementia.ConclusionsThis case series describes the exacerbation of pre-existing psychiatric and cognitive conditions after COVID-19 recovery in 3 older adults with formal neuropsychological evaluation data. Longitudinal investigation of convalescent patients is warranted to better clinically characterize and provide insight into the long-term effects of COVID-19. This will allow further investigation into the pathophysiology regarding the long-term consequences of SARS-CoV-2 infection.FundingNot Applicable.

A case suspected of Alzheimer type dementia showing multimodal (face and voice) person recognition disorder from face and voice

A 90-year-old woman presented with a multimodal (face and voice) person recognition disorder. Although she had moderate general cognitive impairment, her visual cognitive capacity, other than face recognition, was well preserved. She could identify the faces and voices of family members but could not recall the names and voices of relatives whom she met infrequently, famous individuals, or the medical staff. She could remember the first names and some information about prominent individuals when supplied with their surnames. Therefore, we thought that her person-specific semantic memory was intact but she was unable to access it through their faces and voices. MRI revealed predominantly right-sided bilateral anterior temporal lobe and hippocampal atrophy. SPECT images showed decreased blood flow in the bilateral anterior temporal lobes and inferior parietal lobule (heavily and predominantly right-sided), right posterior cingulate gyrus, and precuneus. Progressive person recognition disorder or prosopagnosia has been considered a right temporal variant of frontotemporal lobar degeneration because abnormal behaviors and psychiatric symptoms frequently coexist. However, no such symptoms were observed in this case, therefore we suspected dementia of the Alzheimer type.

Longitudinal clinical and neuroanatomical correlates of memory impairment in motor neuron disease

Memory impairment in motor neuron disease (MND) is still an underrecognized feature and has traditionally been attributed to executive dysfunction. Here, we investigate the rate of memory impairment in a longitudinal cohort of MND patients, its relationship to other cognitive functions and the underlying neuroanatomical correlates. 142 patients with MND and 99 healthy controls (HC) underwent comprehensive neuropsychological testing and structural MRI at 3T up to four times over a period of 18 months. Linear-mixed effects models were fitted to identify changes at baseline and over time in episodic memory function (learning, immediate and delayed recall, recognition), composed cognitive scores (memory, verbal fluency, executive function), and memory-related structural brain regions (hippocampus, entorhinal cortex, parahippocampal gyrus). Associations between episodic memory performance and volumetric or cortical thickness changes of these regions were computed using Pearson's r. Learning, immediate and delayed recall, as well as recognition performance were significantly reduced in MND when compared to controls at baseline. Performances in these subtests improved over time although MND showed less improvement than controls. This relationship did not change when only “classical” ALS patients were considered. Patients with MND showed thinning of the right parahippocampal gyrus (PhG) in comparison to controls that was progressing over time. Bilateral hippocampal atrophy was observed in MND patients with memory impairment after splitting the group according to their overall episodic memory performance, with the right hippocampus shrinking over time. In MND patients, the bilateral hippocampal atrophy was associated with impairment in learning, recall, and recognition at baseline. In contrast, left PhG thinning was associated with a poorer learning performance. These results show that episodic memory impairment in MND is a frequent cognitive dysfunction. Since deficits are not clearly declining with disease course, an early involvement of this cognitive domain in the disease seems probable. The memory performance-dependent atrophy of the hippocampus and PhG provide evidence for a widespread involvement of these non-motor cortical areas in disease pathology.

Social cognition in an adult epilepsy patient with developmental amnesia

ABSTRACT Reports on social cognition in patients with developmental amnesia resulting from bilateral hippocampal lesions are rare, although the link between social cognition and temporal lobe structures is well established. We present the case of a 23-year-old male epilepsy patient, BM, with developmental amnesia due to perinatal cerebral hypoxia. The patient was examined with neuroimaging and neuropsychological methods and compared to IQ-matched patients with epilepsy to control for effects of epilepsy. In addition, we used a test battery that evaluates emotion recognition and theory of mind to study his social cognition abilities. Structural high-resolution magnetic resonance imaging showed bilateral hippocampal atrophy. The comparison to controls showed that, in addition to the well-documented memory disorders in developmental amnesia, BM showed remarkable deficits in 9 out of 17 social cognitive tasks assessing emotion recognition and theory of mind. In contrast, BM’s performance on tasks of executive functions was largely preserved. The relevance of deficits in social cognition for patients with developmental amnesia is discussed.

Hippocampal Shape Is Associated with Memory Deficits in Temporal Lobe Epilepsy.

ObjectiveCognitive problems, especially disturbances in episodic memory, and hippocampal sclerosis are common in temporal lobe epilepsy (TLE), but little is known about the relationship of hippocampal morphology with memory. We aimed to relate hippocampal surface‐shape patterns to verbal and visual learning.MethodsWe analyzed hippocampal surface shapes on high‐resolution magnetic resonance images and the Adult Memory and Information Processing Battery in 145 unilateral refractory TLE patients undergoing epilepsy surgery, a validation set of 55 unilateral refractory TLE patients, and 39 age‐ and sex‐matched healthy volunteers.ResultsBoth left TLE (LTLE) and right TLE (RTLE) patients had lower verbal (LTLE 44 ± 11; RTLE 45 ± 10) and visual learning (LTLE 34 ± 8, RTLE 30 ± 8) scores than healthy controls (verbal 58 ± 8, visual 39 ± 6; p < 0.001). Verbal learning was more impaired the greater the atrophy of the left superolateral hippocampal head. In contrast, visual memory was worse with greater bilateral inferomedial hippocampal atrophy. Postsurgical verbal memory decline was more common in LTLE than in RTLE (reliable change index in LTLE 27% vs RTLE 7%, p = 0.006), whereas there were no differences in postsurgical visual memory decline between those groups. Preoperative atrophy of the left hippocampal tail predicted postsurgical verbal memory decline.InterpretationMemory deficits in TLE are associated with specific morphological alterations of the hippocampus, which could help stratify TLE patients into those at high versus low risk of presurgical or postsurgical memory deficits. This knowledge could improve planning and prognosis of selective epilepsy surgery and neuropsychological counseling in TLE. ANN NEUROL 2020 ANN NEUROL 2020;88:170–182

Central Nervous System Infection-Related Isolated Hippocampal Atrophy as Another Subtype of Medial Temporal Lobe Epilepsy with Hippocampal Atrophy: A Comparison to Conventional Medial Temporal Lobe Epilepsy with Hippocampal Atrophy.

Background and PurposeHippocampal atrophy (HA) resulting from a central nervous system (CNS) infection might be a relevant lesion responsible for the clinical characteristics of medial temporal lobe epilepsy.MethodsThe clinical characteristics of 54 patients with CNS infection-related medial temporal lobe epilepsy (MTLE) with isolated HA (CNS infection group) and 155 patients with conventional MTLE with HA (conventional group) were compared retrospectively. CNS infection alone and bilateral involvement of the HA were analyzed as prognostic factors, in addition to the detailed clinical characteristics, such as limbic aura and the presence and proportion of each type of automatism, between the two groups, and both medical and surgical prognoses were separately considered. A logistic regression analysis was performed.ResultsA statistical analysis including all clinical factors, including CNS infection with bilateral HA, did not reveal significant differences between the two groups. An analysis comparing the prognosis of the two groups based on good or poor prognosis among patients who received medical treatment and good or poor outcomes among patients who received surgical treatment did not produce significant differences.ConclusionsIn addition to bilateral HA, CNS infection alone was not a poor prognostic factor for the CNS infection-related epilepsy with HA group compared with the conventional MTLE with HA group. Based on these negative results, HA is a plausible and relevant lesion with similar clinical characteristics to HA in patients with conventional MTLE. Therefore, CNS infection-related MTLE with isolated HA might represent another subtype of MTLE with HA with a different etiology.

Network, clinical and sociodemographic features of cognitive phenotypes in temporal lobe epilepsy

This study explored the taxonomy of cognitive impairment within temporal lobe epilepsy and characterized the sociodemographic, clinical and neurobiological correlates of identified cognitive phenotypes. 111 temporal lobe epilepsy patients and 83 controls (mean ages 33 and 39, 57% and 61% female, respectively) from the Epilepsy Connectome Project underwent neuropsychological assessment, clinical interview, and high resolution 3T structural and resting-state functional MRI. A comprehensive neuropsychological test battery was reduced to core cognitive domains (language, memory, executive, visuospatial, motor speed) which were then subjected to cluster analysis. The resulting cognitive subgroups were compared in regard to sociodemographic and clinical epilepsy characteristics as well as variations in brain structure and functional connectivity. Three cognitive subgroups were identified (intact, language/memory/executive function impairment, generalized impairment) which differed significantly, in a systematic fashion, across multiple features. The generalized impairment group was characterized by an earlier age at medication initiation (P < 0.05), fewer patient (P < 0.001) and parental years of education (P < 0.05), greater racial diversity (P < 0.05), and greater number of lifetime generalized seizures (P < 0.001). The three groups also differed in an orderly manner across total intracranial (P < 0.001) and bilateral cerebellar cortex volumes (P < 0.01), and rate of bilateral hippocampal atrophy (P < 0.014), but minimally in regional measures of cortical volume or thickness. In contrast, large-scale patterns of cortical-subcortical covariance networks revealed significant differences across groups in global and local measures of community structure and distribution of hubs. Resting-state fMRI revealed stepwise anomalies as a function of cluster membership, with the most abnormal patterns of connectivity evident in the generalized impairment group and no significant differences from controls in the cognitively intact group. Overall, the distinct underlying cognitive phenotypes of temporal lobe epilepsy harbor systematic relationships with clinical, sociodemographic and neuroimaging correlates. Cognitive phenotype variations in patient and familial education and ethnicity, with linked variations in total intracranial volume, raise the question of an early and persisting socioeconomic-status related neurodevelopmental impact, with additional contributions of clinical epilepsy factors (e.g., lifetime generalized seizures). The neuroimaging features of cognitive phenotype membership are most notable for disrupted large scale cortical-subcortical networks and patterns of functional connectivity with bilateral hippocampal and cerebellar atrophy. The cognitive taxonomy of temporal lobe epilepsy appears influenced by features that reflect the combined influence of socioeconomic, neurodevelopmental and neurobiological risk factors.

CSF sTREM2 and Tau Work Together in Predicting Increased Temporal Lobe Atrophy in Older Adults.

Neuroinflammation may be a key factor in brain atrophy in aging and age-related neurodegenerative disease. The objective of this study was to test the association between microglial expression of soluble Triggering Receptor Expressed on Myeloid Cells 2 (sTREM2), as a measure of neuroinflammation, and brain atrophy in cognitively unimpaired older adults. Brain magnetic resonance imagings (MRIs) and cerebrospinal fluid (CSF) sTREM2, total tau (t-tau), phosphorylated181 tau (p-tau), and Aβ42 were analyzed in 115 cognitively unimpaired older adults, classified according to the A/T/(N)-framework. MRIs were repeated after 2 (n = 95) and 4 (n = 62) years. High baseline sTREM2 was associated with accelerated cortical thinning in the temporal cortex of the left hemisphere, as well as bilateral hippocampal atrophy, independently of age, Aβ42, and tau. sTREM2-related atrophy only marginally increased with biomarker positivity across the AD continuum (A-T- #x2292; A+T- #x2292; A+T+) but was significantly stronger in participants with a high level of p-tau (T+). sTREM2-related cortical thinning correlated significantly with areas of high microglial-specific gene expression in the Allen Human Brain Atlas. In conclusion, increased CSF sTREM2 was associated with accelerated cortical and hippocampal atrophy in cognitively unimpaired older participants, particularly in individuals with tau pathology. This suggests a link between neuroinflammation, neurodegeneration, and amyloid-independent tauopathy.

Long-term Outcomes of Patients With Human Herpesvirus 6 Encephalitis.

Human herpesviruses 6 (HHV-6) A and B cause encephalitis in patients with hematologic malignancies, especially those undergoing allogeneic hematopoietic stem cell transplantation. In this cohort of 10 patients, persistent neurologic deficits associated with moderate to severe bilateral hippocampal atrophy were characteristic long-term findings, despite prolonged antiviral treatment.