Aside from rare case reports, only one study, with 12 patients, has addressed the phenotypic presentation of epilepsy in clinically defined amnestic mild cognitive impairment (aMCI, presumed to ...correspond to the AD prodromal stage): the authors highlighted a pharmacosensitive non-convulsive partial epileptic syndrome most probably related to the temporal or temporo-frontal cortices.
The objective of this study was to verify the existence and the syndromic features of epileptic prodromal AD in a tertiary Memory Clinic.
We conducted a retrospective, single-center study of the electro-radio-clinical features of 13 cases of epileptic prodromal AD patients (3.1% of a cohort of MCI, n = 430 subjects), selected on both clinical criteria and CSF biomarkers.
In our patients, a pharmacosensitive temporal lobe epilepsy syndrome, inaugurating prodromal AD, started at a mean age of 63 years (±12.8 years) and preceded MCI diagnosis by 4 to 7 years. At the stage of aMCI, median MMSE score was 26 and imaging showed mild hippocampal atrophy. After almost one year under treatment, cognitive complaints were not relieved but the MMSE score remained stable at 26 for 11 patients (2 patients were excluded from analysis because of the onset of aphasic or neurovisual symptoms altering MMSE scoring).
Our data, in conjunction with those of the 12 previously described subjects, suggest the existence of a currently unrecognized inaugural epilepsy syndrome of sporadic AD. Such a syndrome could be called the epileptic variant of AD because seizures are its sole feature for more than 2.5 years.
Highlights ► In normal ageing, disturbances in social cognition seem independent of a more general cognitive decline. ► When neurodegeneration spares brain areas underpinning social cognition, this ...ability is unaffected. ► Impairment in social cognition is related to increased vulnerability of the frontal lobes with ageing.
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•TEAs are not associated with significant cortical atrophy according to MRI-based visual rating scales.•TEAs are significantly associated with bilateral or right predominant ...hippocampal calcifications.•Hippocampal calcifications are mainly located in the CA1 subfield of the cornu Ammonis.•Hippocampal calcifications are of probable vascular origin (hippocampal restricted small vessels disease).•Chronic CA1 disruption may explain the ictal and interictal features of TEAs.
The exact etiology of transient epileptic amnesia (TEA) is currently unknown. In older individuals, common neurodegenerative dementias and small-vessel diseases (SVDs) could be major contributors. We examined these hypotheses on the basis of imaging analysis.
In total, 36 TEA patients were compared with 25 healthy controls for (1) cortical atrophic changes (in the mesial temporal, frontal, anterior temporal, and parietal regions) using four established MRI-based visual rating scales, and for (2) SVD evidence using two MRI-based visual rating scales (Fazekas and MARS scores). In 24 TEAs cases, there were also brain CT scans available that were compared with 57 controls for the presence of hippocampal calcifications (HCs).
We did not find significant differences in cortical atrophy between TEAs and controls, nor did we observe a different SVD brain load on MRI. However, TEAs were significantly associated (p < 0.01) with uni- or bilateral CA1-located HCs in half of the patients compared with the controls (less than 20 %).
This study argues in favor of a hippocampal-restricted SVD (as indicated by HCs) as one of the major etiologies of TEA, while neurodegenerative dementias are probably minor causes. It furthermore highlights the pivotal role of the CA1 hippocampal subfield in the pathophysiology of this syndrome.
Background:
Data are needed on long-term effect of natalizumab (NTZ) in relapsing-remitting multiple sclerosis (RRMS).
Objectives:
To evaluate the time of onset of secondary progressive phase in ...patients with an RRMS treated with NTZ and to investigate predictive factors.
Methods:
TYSTEN is an observational study. Patients starting NTZ between 2007 and 2012 were included and followed up until October 2018. Relapses, Expanded Disability Status Scale (EDSS) scores, and results of brain magnetic resonance imaging (MRI) were collected each year. Data were used to estimate the cumulative probability of several poor outcomes such as secondary progressive multiple sclerosis (SPMS) conversion, EDSS worsening, EDSS 4.0, and EDSS 6.0.
Results:
770 patients were included. The mean follow-up duration was 97 months and the mean time exposure to NTZ was 66 months. At 10 years, the cumulative probability of SPMS was 27.7%. Predictive factors for poor outcomes were a ⩾1-point increase in EDSS score from baseline, new T2 lesion or T1 gadolinium-enhancing lesion, the occurrence of relapse at 1 or 2 years and No Evidence of Disease Activity (NEDA-3; no relapse, no new T2 or T1 gadolinium-enhancing lesions, no progression) was a protective factor.
Conclusion:
In our cohort of patients treated with NTZ, poor outcomes were infrequent and are driven by disease activity.
Background
Interleukin 6 (IL-6) is a pleomorphic cytokine that can be found in the cerebrospinal fluid (CSF) in a wide spectrum of inflammatory pathologies of the central nervous system (CNS).
...Objective
Our aim was to characterize the diagnostic significance of CSF IL-6 among various CNS inflammatory diseases with pseudotumoral lesions (CNSID) and primary CNS lymphoma (PCNSL).
Methods
We retrospectively analyzed the CSF IL-6 concentrations in 43 consecutive patients with suspected PCNSL. A total of 28 patients were positively diagnosed with PCNSL and 15 with CNSID. We verified the results with CSF IL-10, an established biomarker for PCNSL.
Results
In the PCNSL group, the median CSF IL-6 concentration was 8 pg/ml, interquartile range (IQR) 5–18.5. For the patients with CNSID, the median concentration was 70 pg/ml, IQR 5–1368. A group comparison showed significantly higher CSF IL-6 levels in patients with CNSID than in those with PCNSL (
p
= 0.032). Moreover, IL-6 was correlated with CSF cell count in the CNSID group (
r
= 0.56,
p
= 0.028), but not in the PCNSL group (
r
= 0.3,
p
= 0.13).
We found significantly higher CSF IL-10 levels in patients with PCNSL than in patients with CNS inflammatory lesions (
p
< 0.001).
Discussion and conclusions
Our study suggests that CSF IL-6 levels could represent, in addition to CSF IL-10, a useful biomarker in the differential diagnosis of CNSID and suspected PCNSL.
To report the clinical, biological, and imaging features and clinical course of a French cohort of patients with glial fibrillary acidic protein (GFAP) autoantibodies.
We retrospectively included all ...patients who tested positive for GFAP antibodies in the CSF by immunohistochemistry and confirmed by cell-based assay using cells expressing human GFAPα since 2017 from 2 French referral centers.
We identified 46 patients with GFAP antibodies. Median age at onset was 43 years, and 65% were men. Infectious prodromal symptoms were found in 82%. Other autoimmune diseases were found in 22% of patients, and coexisting neural autoantibodies in 11%. Tumors were present in 24%, and T-cell dysfunction in 23%. The most frequent presentation was subacute meningoencephalitis (85%), with cerebellar dysfunction in 57% of cases. Other clinical presentations included myelitis (30%) and visual (35%) and peripheral nervous system involvement (24%). MRI showed perivascular radial enhancement in 32%, periventricular T2 hyperintensity in 41%, brainstem involvement in 31%, leptomeningeal enhancement in 26%, and reversible splenial lesions in 4 cases. A total of 33 of 40 patients had a monophasic course, associated with a good outcome at last follow-up (Rankin Score ≤2: 89%), despite a severe clinical presentation. Adult and pediatric features are similar. Thirty-two patients were treated with immunotherapy. A total of 11/22 patients showed negative conversion of GFAP antibodies.
GFAP autoimmunity is mainly associated with acute/subacute meningoencephalomyelitis with prodromal symptoms, for which tumors and T-cell dysfunction are frequent triggers. The majority of patients followed a monophasic course with a good outcome.
Background:
Epidemiologic studies on coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (pwMS) have focused on the first waves of the pandemic until early 2021.
Objectives:
We ...aimed to extend these data from the onset of the pandemic to the global coverage by vaccination in summer 2022.
Methods:
This retrospective, multicenter observational study analyzed COVISEP registry data on reported COVID-19 cases in pwMS between January 2020 and July 2022. Severe COVID-19 was defined as hospitalization or higher severity.
Results:
Among 2584 pwMS with confirmed/highly suspected COVID-19, severe infection rates declined from 14.6% preomicron wave to 5.7% during omicron wave (p < 0.001). Multivariate analysis identified age (odds ratio (OR) = 1.43, 95% confidence interval (CI) = 1.25–1.64 per 10 years), male sex (OR = 2.01, 95% CI = 1.51–2.67), obesity (OR = 2.36, 95% CI = 1.52–3.68), cardiac comorbidities (OR = 2.36, 95% CI = 1.46–3.83), higher Expanded Disability Status Scale (EDSS) scores (OR = 2.09, 95% CI = 1.43–3.06 for EDSS 3–5.5 and OR = 4.53, 95% CI = 3.04–6.75 for EDSS ⩾6), and anti-CD20 therapies (OR = 2.67, 95% CI = 1.85–3.87) as risk factors for COVID-19 severity. Vaccinated individuals experienced less severe COVID-19, whether on (risk ratio (RR) = 0.64, 95% CI = 0.60–0.69) or off (RR = 0.32, 95% CI = 0.30–0.33) anti-CD20.
Discussion:
In pwMS, consistent risk factors were anti-CD20 therapies and neurological disability, emerging as vital drivers of COVID-19 severity regardless of wave, period, or vaccination status.
Our objective was to evaluate the relationship between cannabis use and ischemic stroke in a young adult population.
Forty-eight consecutive young patients admitted for acute ischemic stroke ...participated in the study. First-line screening was performed, including blood tests, cardiovascular investigations, and urine analysis for cannabinoids. If no etiology was found, 3D rotational angiography and cerebrospinal fluid analysis were performed. A control was planned through neurovascular imaging within 3 to 6 months.
In this series, there was multifocal intracranial stenosis associated with cannabis use in 21% (n=10).
Multifocal angiopathy associated with cannabis consumption could be an important cause of ischemic stroke in young people.
Microduplications of the 17q21.31 chromosomal region encompassing the
MAPT
gene, which encodes the Tau protein, were identified in patients with a progressive disorder initially characterized by ...severe memory impairment with or without behavioral changes that can clinically mimic Alzheimer disease. The unique neuropathological report showed a primary tauopathy, which could not be unanimously classified in a given known subtype, showing both 4R- and 3R-tau inclusions, mainly within temporal cortical subregions and basal ganglia, without amyloid deposits. Recently, two subjects harboring the same duplication were reported with an atypical extrapyramidal syndrome and gait disorder. To decipher the phenotypic spectrum associated with
MAPT
duplications, we studied ten carriers from nine families, including two novel unrelated probands, gathering clinical (
n
= 10), cerebrospinal fluid (
n
= 6), MRI (
n
= 8), dopamine transporter scan (
n
= 4), functional (
n
= 5), amyloid (
n
= 3) and Tau-tracer (
n
= 2) PET imaging data as well as neuropathological examination (
n
= 4). Ages at onset ranged from 37 to 57 years, with prominent episodic memory impairment in 8/10 patients, associated with behavioral changes in four, while two patients showed atypical extrapyramidal syndrome with gait disorder at presentation, including one with associated cognitive deficits. Amyloid imaging was negative but Tau imaging showed significant deposits mainly in both mesiotemporal cortex. Dopaminergic denervation was found in 4/4 patients, including three without extrapyramidal symptoms. Neuropathological examination exclusively showed Tau-immunoreactive lesions. Distribution, aspect and 4R/3R tau aggregates composition suggested a spectrum from predominantly 3R, mainly cortical deposits well correlating with cognitive and behavioral changes, to predominantly 4R deposits, mainly in the basal ganglia and midbrain, in patients with prominent extrapyramidal syndrome. Finally, we performed in vitro seeding experiments in HEK-biosensor cells. Morphological features of aggregates induced by homogenates of three
MAPT
duplication carriers showed dense/granular ratios graduating between those induced by homogenates of a Pick disease and a progressive supranuclear palsy cases. These results suggest that
MAPT
duplication causes a primary tauopathy associated with diverse clinical and neuropathological features.
In the absence of a simple validated instrument to screen for cognitive impairment among illiterate Lebanese older adults, the aims of this study were to validate an Arabic version of the Test of ...Nine Images (A-TNI93) adapted by the Working Group on Dementia at Saint Joseph University: Groupe de Travail sur les Démences de l'Univesité Saint Joseph (GTD-USJ) for illiterate older Lebanese and to establish normative data.
A national population-based sample of 332 community-dwelling illiterate Lebanese aged 55 years and older was administered the A-TNI93 (GTD-USJ) scoring free and overall recall. The sample is part of a larger national sample (1342 participants) used to validate an Arabic version of the Mini-Mental State Examination already reported. Reproducibility, sensitivity, specificity, and area under the curve of the A-TNI93 (GTD-USJ) scoring to detect cognitive impairment according to Clinical Dementia Rating (CDR) as the gold standard were measured. Normative data were established among 188 cognitively normal participants.
A threshold score of six on free recall (FR) provided a sensitivity of 66.7% and a specificity of 90.5%. The area under the curve was 0.93. By taking either scores, that is, a FR ≤ 6 or a total recall ≤ 8, the A-TNI93 (GTD-USJ) slightly improved dementia case detection with a sensitivity of 70.8% and a specificity of 88%. Normative data illustrate the distribution of cognitive performance among illiterate older adults.
Compared to the CDR requiring physician's competence, the A-TNI93 (GTD-USJ) is a valid Arabic adaptation to screen for cognitive impairment among illiterate Lebanese older adults.
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