Two neurologic facets of CTLA4-related haploinsufficiency

ObjectiveTo describe the clinical and radiologic neurologic characteristics of patients with cytotoxic T-lymphocyte antigen-4 (CTLA4) haploinsufficiency.MethodsThree patients from 2 families had neurologic manifestations in the context of CTLA4 haploinsufficiency. Their clinical and MRI findings are presented.ResultsA 16-year-old boy with a previous diagnosis of combined immunodeficiency presented with severe recurrent episodes of headaches, motor deficit, and seizures associated with waxing and waning gadolinium-enhancing FLAIR cortical/juxtacortical hyperintensities. His sister, who also had combined immunodeficiency, had a brain MRI when she was aged 13 years due to recent headaches and transient right hemianopsia. It revealed a gadolinium-enhancing left occipital white matter hyperintensity. Another 49-year-old woman had progressive visual loss and cerebellar ataxia in the context of recurrent pulmonary infections. All 3 patients were found to have inherited CTLA4 haploinsufficiency. Patient 1's general condition and neurologic manifestations were completely controlled with abatacept (CTLA4-Ig).ConclusionsThese cases suggest that in addition to the variable clinical penetrance and wide spectrum of CTLA4 haploinsufficiency, its neurologic spectrum is broad, ranging from recurrent tumefactive lesions to progressive deficits including cerebellar ataxia and optic atrophy with leukoencephalopathy. These phenotypes must be recognized, and should lead to a complete immunologic workup, because potentially effective targeted immunotherapy exists.

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Retrospective Observational Study of Brain MRI Findings in Patients with Acute SARS-CoV-2 Infection and Neurologic Manifestations

Radiology ◽

10.1148/radiol.2020202422 ◽

2020 ◽

Vol 297 (3) ◽

pp. E313-E323 ◽

Cited By ~ 14

Author(s):

Lydia Chougar ◽

Natalia Shor ◽

Nicolas Weiss ◽

Damien Galanaud ◽

Delphine Leclercq ◽

...

Keyword(s):

Observational Study ◽

Brain Mri ◽

Retrospective Observational Study ◽

Neurologic Manifestations ◽

Mri Findings

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Cerebrospinal fluid features in COVID-19 patients with neurologic manifestations: correlation with brain MRI findings in 58 patients

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa745 ◽

2020 ◽

Author(s):

François Lersy ◽

Ilies Benotmane ◽

Julie Helms ◽

Olivier Collange ◽

Maleka Schenck ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Clinical Laboratory ◽

Brain Mri ◽

Oligoclonal Bands ◽

Neurologic Manifestations ◽

Neurological Manifestations ◽

Rt Pcr ◽

Mri Findings ◽

Leptomeningeal Enhancement ◽

Csf Analysis

Abstract Background Neurological manifestations are common in patients with COVID-19, but little is known about pathophysiological mechanisms. In this single-center study, we describe neurological manifestations of 58 patients, regarding cerebrospinal fluid (CSF) analysis and neuroimaging findings. Methods 58 COVID-19 patients with neurologic manifestations and SARS-CoV-2 RT-PCR screening on CSF analysis were included. Clinical, laboratory, and brain MRI data were retrospectively collected and analyzed. Results Patients were mostly men (66%) with a median age of 62 years. Encephalopathy was frequent (81%), followed by a pyramidal dysfunction (16%), seizures (10%), and headaches (5%). Protein and albumin levels in CSF were increased in 38% and 23%, respectively. A total of 40% of patients displayed an elevated albumin quotient suggesting impaired blood-brain barrier integrity. CSF-specific IgG oligoclonal band was found in five (11%) cases, suggesting an intrathecal synthesis of IgG, and 26 (55%) patients presented identical oligoclonal bands in serum and CSF. Four (7%) patients harbored a positive SARS-CoV-2 RT-PCR in CSF. Regarding brain MRI, 20 (38%) patients presented leptomeningeal enhancement. Conclusions Brain MRI abnormalities, especially leptomeningeal enhancement, and increased inflammatory markers in CSF are frequent in patients with neurological manifestations related to COVID-19, whereas SARS-CoV 2 detection in CSF remained scanty.

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A wide spectrum of clinical and brain MRI findings in patients with SLC19A3mutations

BMC Medical Genetics ◽

10.1186/1471-2350-11-171 ◽

2010 ◽

Vol 11 (1) ◽

Cited By ~ 60

Author(s):

Kenichiro Yamada ◽

Kiyokuni Miura ◽

Kenju Hara ◽

Motomasa Suzuki ◽

Keiko Nakanishi ◽

...

Keyword(s):

Wide Spectrum ◽

Brain Mri ◽

Mri Findings

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Abstract 169: Circulating Il-6 And Il-18 Levels Are Associated With The Risk Of Incident Dementia In Patients With Vascular Risk Factors

Stroke ◽

10.1161/str.44.suppl_1.a169 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Kaori Miwa ◽

Makiko Tanaka ◽

Shuhei Okazaki ◽

Shigetaka Furukado ◽

Manabu Sakaguchi ◽

...

Keyword(s):

Risk Factors ◽

Brain Atrophy ◽

Inflammatory Markers ◽

Brain Mri ◽

Vascular Risk Factors ◽

White Matter Hyperintensity ◽

Vascular Risk ◽

Mri Findings ◽

Apoe4 Allele ◽

Incident Dementia

Background and Purpose: Association between circulating inflammatory marker and future dementia has not been fully investigated. To what extent inflammatory markers impact future dementia beyond small vessel disease (SVD) and brain atrophy on MRI is unknown. We sought to determine the predictive value of circulating inflammation marker (high-sensitivity C-reactive protein [hsCRP], interleukin [IL]-6, and IL-18), when controlling for MRI measures of SVD (lacunar, white matter hyperintensity [WMH]) and brain atrophy on the risk of dementia. Methods: We enrolled 480 outpatients (median 68 years, male 58%, 12.8±2.4 years of schooling ) who had vascular risk factors but without dementia. At baseline, demographic information, brain MRI, and cognitive function testing were performed. We also measured hsCRP, IL-6, and IL-18. Baseline MRI was used to determine SVD (lacunar and WMH) and atrophy (cortical and subcortical). Cox proportional hazards analysis was performed as predictors of dementia with adjusting for age, gender, APOE4 allele, educational level, history of clinical stroke, conventional vascular risk factors, baseline Mini-Mental State Examination score and MRI-findings. Results: At end of follow-up (median 7.5 years duration), 40 patients had dementia (Alzheimer disease:21 patients, vascular dementia:16 patients, other type dementia:3 patients) In the age, gender, education level, and APOE4 allele-adjusted models, WMH severity, number of lacunar, atrophy, previous stroke, smoking and baseline MMSE-score were associated with incident dementia. Among inflammatory markers, both IL-6 and IL-18, but not hsCRP, were associated with dementia (IL-6; HR:2.10, 95% CI [1.21-3.58], IL-18; HR:3.32, 95% CI [1.52 -7.28], hsCRP; HR:1.08, 95% CI [0.80-1.46]) (per 1-SD increase in log-transformed inflammatory markers). These associations of both IL-6 and IL-18 with dementia remained significant even after additional adjusting for MRI-findings and confounding variables Conclusion: Our longitudinal study showed that both IL-6 and IL-18 levels are independently related to the risk of dementia in patients with vascular risk factors. Our results support the hypothesis that inflammation exerts deleterious effects on dementia incidence.

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BRAIN MRI FINDINGS IN ACUTE HYPERAMMONEMIC ENCEPHALOPATHY SECONDARY TO ISCHEMIC HEPATITIS: CASE REPORT AND REVIEW OF THE LITERATURE

Romanian Journal of Neurology ◽

10.37897/rjn.2016.1.5 ◽

2016 ◽

Vol 15 (1) ◽

pp. 35-38

Author(s):

Ana-Maria Vladila ◽

◽

Dan-Andrei Mitrea ◽

Sanda Nica ◽

Gabriela Mihailescu ◽

...

Keyword(s):

Wide Spectrum ◽

Adult Population ◽

Brain Mri ◽

Brain Magnetic Resonance Imaging ◽

Review Of The Literature ◽

Resonance Imaging ◽

Mri Findings ◽

Hyperammonemic Encephalopathy ◽

Ischemic Hepatitis ◽

Hepatitis Case

Acute encephalopathy is frequently seen in Neurology and Internal Medicine Departments, it makes for a wide spectrum of neuropsychiatric abnormalities, but its brain magnetic resonance imaging appearance in the adult population is not well recognised. We present the case of an acute hyperammonemic encephalopathy in the setting of ischemic hepatitis secondary to global heart failure and its MRI findings with a review of the literature.

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Brain MRI-findings in Ph - negative myeloproliferative disorders

Terapevticheskii arkhiv ◽

10.26442/00403660.2019.07.000329 ◽

2019 ◽

Vol 91 (7) ◽

pp. 29-34 ◽

Cited By ~ 2

Author(s):

M M Tanashyan ◽

A L Melikyan ◽

P I Kuznetsova ◽

A A Raskurazhev ◽

A A Shabalina ◽

...

Keyword(s):

Cerebrovascular Disease ◽

Sinus Thrombosis ◽

Cerebral Arteries ◽

Brain Mri ◽

Myeloproliferative Disorders ◽

Cerebral Venous Sinus Thrombosis ◽

Mri Findings ◽

Cerebral Lesions ◽

Cerebrovascular Pathology ◽

Underlying Mechanisms

Myeloproliferative disorders (MPD) are accompanied by a high proportion of thrombotic complications, which may lead to cerebrovascular disease (CVD). Aim. To describe MRI-findings in patients with Ph - negative MPD and evaluate any cerebrovascular disease. Materials and methods. We included 104 patients with Ph - negative MPD (age varied between 20 and 58) with clinical correlates of cerebrovascular pathology. Results. Brain MRI showed post - stroke lesions in 20% of patients (7 hemispheric infarcts due to thrombotic occlusion of one of the large cerebral arteries, 14 - cortical infarcts). 37 patients (36%) had vascular cerebral lesions. Cerebral venous sinus thrombosis occurred in 5 patients - in 7% (n=3) of patients with polycythemia vera and 5% (n=2) - in patients with essential thrombocythemia. The incidence of vascular cerebral lesions was associated with higher levels of the following: erythrocyte, platelet count, fibrinogen, and with the decrease in fibrinolytic activity, as well. Conclusion. The pioneering results of the study include the description and analysis of brain MRI-findings in patients with Ph - negative MPD. The underlying mechanisms of cerebrovascular pathology in these patients are associated with certain blood alterations (particularly, hemorheology) which present a major risk factor.

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Comparisons of clinical characteristics, brain MRI findings, and responses to epidural blood patch between spontaneous intracranial hypotension and post-dural puncture headache: retrospective study

BMC Neurology ◽

10.1186/s12883-021-02279-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Gha-Hyun Lee ◽

Jiyoung Kim ◽

Hyun-Woo Kim ◽

Jae Wook Cho

Keyword(s):

Intracranial Hypotension ◽

Dural Puncture ◽

Epidural Blood Patch ◽

Brain Mri ◽

Spontaneous Intracranial Hypotension ◽

Vein Of Galen ◽

Mri Findings ◽

Post Dural Puncture Headache ◽

Straight Sinus ◽

Blood Patch

Abstract Background Spontaneous intracranial hypotension and post-dural puncture headache are both caused by a loss of cerebrospinal fluid but present with different pathogeneses. We compared these two conditions concerning their clinical characteristics, brain imaging findings, and responses to epidural blood patch treatment. Methods We retrospectively reviewed the records of patients with intracranial hypotension admitted to the Neurology ward of the Pusan National University Hospital between January 1, 2011, and December 31, 2019, and collected information regarding age, sex, disease duration, hospital course, headache intensity, time to the appearance of a headache after sitting, associated phenomena (nausea, vomiting, auditory symptoms, dizziness), number of epidural blood patch treatments, and prognosis. The brain MRI signs of intracranial hypotension were recorded, including three qualitative signs (diffuse pachymeningeal enhancement, venous distention of the lateral sinus, subdural fluid collection), and six quantitative signs (pituitary height, suprasellar cistern, prepontine cistern, mamillopontine distance, the midbrain-pons angle, and the angle between the vein of Galen and the straight sinus). Results A total of 105 patients (61 spontaneous intracranial hypotension patients and 44 post-dural puncture headache patients) who met the inclusion criteria were reviewed. More patients with spontaneous intracranial hypotension required epidural blood patch treatment than those with post-dural puncture headache (70.5% (43/61) vs. 45.5% (20/44); p = 0.01) and the spontaneous intracranial hypotension group included a higher proportion of patients who underwent epidural blood patch treatment more than once (37.7% (23/61) vs. 13.6% (6/44); p = 0.007). Brain MRI showed signs of intracranial hypotension in both groups, although the angle between the vein of Galen and the straight sinus was greater in the post-dural puncture headache group (median [95% Confidence Interval]: 85° [68°-79°] vs. 74° [76°-96°], p = 0.02). Conclusions Patients with spontaneous intracranial hypotension received more epidural blood patch treatments and more often needed multiple epidural blood patch treatments. Although both groups showed similar brain MRI findings, the angle between the vein of Galen and the straight sinus differed significantly between the groups.

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Genetic Neonatal-Onset Epilepsies and Developmental/Epileptic Encephalopathies with Movement Disorders: A Systematic Review

International Journal of Molecular Sciences ◽

10.3390/ijms22084202 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4202

Author(s):

Carlotta Spagnoli ◽

Carlo Fusco ◽

Antonio Percesepe ◽

Vincenzo Leuzzi ◽

Francesco Pisani

Keyword(s):

Movement Disorders ◽

Time Course ◽

Neonatal Period ◽

Age Of Onset ◽

Brain Mri ◽

Neonatal Seizure ◽

Mri Findings ◽

Epileptic Encephalopathies ◽

Pathogenic Variants ◽

Neonatal Onset

Despite expanding next generation sequencing technologies and increasing clinical interest into complex neurologic phenotypes associating epilepsies and developmental/epileptic encephalopathies (DE/EE) with movement disorders (MD), these monogenic conditions have been less extensively investigated in the neonatal period compared to infancy. We reviewed the medical literature in the study period 2000–2020 to report on monogenic conditions characterized by neonatal onset epilepsy and/or DE/EE and development of an MD, and described their electroclinical, genetic and neuroimaging spectra. In accordance with a PRISMA statement, we created a data collection sheet and a protocol specifying inclusion and exclusion criteria. A total of 28 different genes (from 49 papers) leading to neonatal-onset DE/EE with multiple seizure types, mainly featuring tonic and myoclonic, but also focal motor seizures and a hyperkinetic MD in 89% of conditions, with neonatal onset in 22%, were identified. Neonatal seizure semiology, or MD age of onset, were not always available. The rate of hypokinetic MD was low, and was described from the neonatal period only, with WW domain containing oxidoreductase (WWOX) pathogenic variants. The outcome is characterized by high rates of associated neurodevelopmental disorders and microcephaly. Brain MRI findings are either normal or nonspecific in most conditions, but serial imaging can be necessary in order to detect progressive abnormalities. We found high genetic heterogeneity and low numbers of described patients. Neurological phenotypes are complex, reflecting the involvement of genes necessary for early brain development. Future studies should focus on accurate neonatal epileptic phenotyping, and detailed description of semiology and time-course, of the associated MD, especially for the rarest conditions.

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Delayed post-hypoxic leukoencephalopathy: Case report

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.1654 ◽

2017 ◽

Vol 41 (S1) ◽

pp. s839-s839 ◽

Cited By ~ 1

Author(s):

M. Solerdelcoll Arimany ◽

M. Garriga ◽

E. Parellada

Keyword(s):

Neuropsychiatric Symptoms ◽

Brain Mri ◽

Clinical History ◽

Good Prognosis ◽

Mri Findings ◽

The Mean ◽

Competing Interest ◽

Weighted Sequences ◽

Direct Toxicity ◽

Progressive Cognitive Impairment

IntroductionDelayed post-hypoxic leukoencephalopathy (DPHL) is an underrecognized syndrome of delayed demyelination, where patients manifest neuropsychiatric symptoms after a period of 2–40 days of apparent recovery from a cerebral hypo-oxygenation episode.ObjectivesWe report a case of a patient who successfully recovered from an overdose of heroin, but then suffered a delayed abrupt neurological deterioration.AimsTo improve assessment and recognition of DPHL.MethodsAn adequate retrospective collection of clinical data and nonsystematic review of the literature was performed.ResultsA 43-year-old male with schizoaffective disorder who attempted suicide with an overdose of heroin, was successfully revived and return to his previously mental status, but 3 weeks after, he abruptly developed progressive cognitive impairment with akinetic mutism and ataxia. He was admitted to our acute psychiatric unit after brain CT and chemistry analyses were unremarkable. Brain MRI showed diffusely symmetric hyperintensity in the white matter (WM), pronominally the periventricular WM, on FLAIR and T2 weighted sequences. At 16 weeks postoverdose, he presented improvement both cognitive and motor symptoms, lasting deficits in frontal-executive functions.DiscussionDPHL is characterized by similar clinical and neuroimaging features regardless of the initial insult. The mean lucid interval coincides with the replacement half-life for myelin related lipids and proteins. Prolonged mild-to-moderate hypo-oxygenation of WM is thought to disrupt myelin turnover. It appears probable that these were responsible for DPHL in our patient rather than a direct toxicity.ConclusionDPHL can be diagnosed when clinical history, laboratory assessments and MRI findings are concordant. DPHL requires extensive support care and carries a relatively good prognosis.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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