Brain MRI Findings and Neuro-Psychiatric Involvement in Paroxysmal Nocturnal Hemoglobinuria (PNH)

Abstract PNH is a rare disorder characterized by hemolytic anemia, marrow failure and thrombosis, due to a deficiency in GPI-anchored proteins. Thrombotic events in PNH are commonly described in hepatic, portal, mesenteric, splenic, and renal veins, along with anecdotic case reports of cerebral venous sinus thrombosis and arterial ischemic strokes. This study was aimed at investigate brain involvement in 19 asymptomatic PNH patients by non-enhanced cerebral magnetic resonance imaging (MRI), and by intracranial arterial and venous angio-MRI. Neuroradiological findings were completed with a neuro-psychiatric evaluation, and correlated with clinical/hematologic features and therapy. Seventeen out of 19 patients were classical hemolytic (63% transfusion dependent before treatment with eculizumab and 1 patient also after), and 2 PNH in the context of aplastic anemia (all transfusion-dependent until treatment with ATG-CyA). Median age at diagnosis was 44 years (range 17-80); asthenia and dyspnea on exertion were present in all patients, abdominal pain in 8, and a thrombotic event in 4. Median Hb was 9.6 g/dL (range 6.7-12.9), LDH 3.7-fold (range 1.2-16.3) over upper limit of normal (ULN), and 73% of patients displayed a clone size greater than 50% GPI negative cells; 10/19 of patients were on eculizumab at the moment of the study. On MRI, 11 subjects showed pathological findings: 9 cases displayed white matter (WM) abnormalities related to chronic ischemic small vessel disease, of whom 6 periventricular WM vascular degeneration, and 8 deep WM focal chronic ischemic lesions (5 cases have both sites involved). Moreover, 1 subject showed a focal abnormality >5 mm and 5 subjects a score > 4 as evaluated in WM and basal ganglia by the age related white matter changes (ARWMC) scale. No subject displayed active or previous bleeding, nor were focal alterations of the basal nuclei by the ARWMC scale found. Two patients (80 and 81 yrs) showed atrophy of the cerebral hemispheres. Regarding vascular abnormalities, one subject had hypoplastic left transverse sinus with irregularities in the sinus wall, suspected for prior partial venous thrombosis. Three further cases displayed hypoplastic transverse sinus associated with collateral draining cortical veins, indistinguishable from anatomical variants. Intracranial artery stenosis or aneurysm, and Moya-Moya like alterations were not observed. Finally, cerebral MRI was unremarkable in 8/19 subjects. By comparing patients with or without any MRI abnormality (WM and vascular alterations), mean age was significantly higher in the former (60+17 vs 43+8 yrs, mean+SD, p<0.05), whereas blood counts, hemolytic markers and clone size showed no remarkable differences. Hemoglobin at diagnosis was slightly lower (9.5+1.5 vs 9.9+1.6 g/dL, mean+SD), and LDH greater (5.8+4.4 vs 4.1+2.9 over ULN, mean+SD) in subjects who displayed MRI abnormalities. Moreover, individual hemoglobin levels negatively correlated with the ARWMC score (r=-0.45, p<0.05). No relationship was found between history of abdominal pain/thrombosis and MRI pathological findings. Likewise, MRI abnormalities were not correlated with disease duration. As regards therapy with eculizumab, a pathological MRI was found in 6/10 subjects under treatment and in 5/9 without; the sole significant vascular alteration was detected in a patient under treatment. Neurological examination was unremarkable in all patients but one, who complained of progressive rest tremor in his left arm and leg (twelve years after PNH diagnosis), and was diagnosed with possible Parkinson disease. Previous history of neurological disorders was observed in 3 patients: one typical transient global amnesia (at the age of 60), one seizures (at 5 years), and one headache before the diagnosis of PNH. Regarding psychiatric evaluation, 3/18 patients had a psychiatric disorder according to structured clinical interview for axis I DSM-IV-TR disorders (1 generalized anxiety disorder, 1 bipolar disorder type 2, and 1 adjustment disorder as a consequence of PNH diagnosis). No relationship was observed between MRI findings and neuro-psychiatric assessment. In conclusion, brain MRI revealed chronic ischemic and vascular lesions in 58% of asymptomatic PNH patients. Brain MRI is advisable at diagnosis and during the course of the disease, and WM lesion burden may be useful in the decision to start therapy. Disclosures Barcellini: Agios: Consultancy.

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Volume of white matter hyperintensities increases with blood pressure in patients with hypertension

Journal of International Medical Research ◽

10.1177/0300060519858023 ◽

2019 ◽

Vol 47 (8) ◽

pp. 3681-3689 ◽

Cited By ~ 2

Author(s):

Yu Zhao ◽

Zunyu Ke ◽

Wenbo He ◽

Zhiyou Cai

Keyword(s):

Blood Pressure ◽

White Matter ◽

White Matter Hyperintensities ◽

Clinical Analysis ◽

Primary Diagnosis ◽

Mri Findings ◽

Scale Scores ◽

History Of ◽

Magnetic Resonance Imaging Mri ◽

Fazekas Scale

Objective Hypertension is a risk factor for development of white matter hyperintensities (WMHs). However, the relationship between hypertension and WMHs remains obscure. We sought to clarify this relationship using clinical data from different regions of China. Methods We analyzed the data of 333 patients with WMHs in this study. All included patients underwent conventional magnetic resonance imaging (MRI) examination. A primary diagnosis of WMHs was made according to MRI findings. The volume burden of WMHs was investigated using the Fazekas scale, which is widely used to rate the degree of WMHs. We conducted retrospective clinical analysis of the data in this study. Results Our findings showed that WMHs in patients with hypertension were associated with diabetes, cardiovascular diseases, history of cerebral infarct, and plasma glucose and triglyceride levels. Fazekas scale scores for WMHs increased with increased blood pressure values in patients with hypertension. Conclusion This analysis indicates that hypertension is an independent contributor to the prevalence and severity of WMHs.

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Full Recovery From Cocaine-Induced Toxic Leukoencephalopathy: Emphasizing the Role of Neuroinflammation and Brain Edema

Journal of Investigative Medicine High Impact Case Reports ◽

10.1177/2324709619868266 ◽

2019 ◽

Vol 7 ◽

pp. 232470961986826 ◽

Cited By ~ 1

Author(s):

Edward C. Mader ◽

Alexander B. Ramos ◽

Roberto A. Cruz ◽

Lionel A. Branch

Keyword(s):

White Matter ◽

Time Course ◽

Brain Mri ◽

White Matter Lesions ◽

Psychomotor Retardation ◽

Full Recovery ◽

White Matter Disease ◽

Mri Findings ◽

Prognostic Information ◽

Toxic Leukoencephalopathy

Toxic leukoencephalopathy (TL) is characterized by white matter disease on magnetic resonance imaging (MRI) and evidence of exposure to a neurotoxic agent. We describe a case of cocaine-induced TL in which extensive white matter disease did not preclude full recovery. A 57-year-old man with substance abuse disorder presented with a 5-day history of strange behavior. On admission, he was alert but had difficulty concentrating, psychomotor retardation, and diffuse hyperreflexia. Brain MRI revealed confluent subcortical white matter hyperintensities with restricted diffusion in some but not in other areas. Electroencephalography (EEG) showed mild diffuse slowing. Blood tests were normal except for mild hyperammonemia. Urine screen was positive for cocaine and benzodiazepine but quantitative analysis was significant only for cocaine. Prednisone 60-mg qd was initiated on day 4, tapered over a 5-day period, and discontinued on day 9. He was discharged after 3 weeks. Cognitive function returned to normal 2 weeks after discharge. Five months later, neurologic exam and EEG were normal and MRI showed near-100% resolution of white matter lesions. TL has been attributed to white matter ischemia/hypoxia resulting in demyelination/axonal injury. The clinical, EEG, and MRI findings and time course of recovery of our patient suggest that cocaine-induced inflammation/edema resulted in TL but not in ischemic/hypoxic injury. While inflammation/edema may have regressed when cocaine was discontinued, we cannot exclude a role for prednisone in protecting the patient from the ischemic/hypoxic sequelae of inflammation/edema. MRI is indispensable for diagnosing TL but EEG may provide additional useful diagnostic and prognostic information.

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Psychological distress in patients suffering from femoral head osteonecrosis, with and without white matter lesions: clinical characteristics and personality traits

European Psychiatry ◽

10.1016/s0924-9338(11)72582-2 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 877-877

Author(s):

O. Mouzas ◽

M.N. Papaliaga ◽

A. Zibis ◽

G. Hadjigeorgiou ◽

N. Angelopoulos ◽

...

Keyword(s):

Psychological Distress ◽

White Matter ◽

Femoral Head ◽

Brain Mri ◽

General Health Questionnaire ◽

White Matter Lesions ◽

Self Report ◽

Cerebral White Matter ◽

Mri Findings ◽

Femoral Head Osteonecrosis

BackgroundThe aim of the present study was to investigate clinical parameters in relation to personality characteristics and psychopathology, in patients with non traumatic osteonecrosis of the femoral head (ONFH), with and without cerebral white matter lesions (WML).MethodsSixty seven patients participated in the study, 48 males and 19 females. The mean age was 37.6 years (SD 10.92, range: 15–61). Seventy five healthy individuals age and sex matched, served as controls. Socio-demographic information, clinical data and brain MRI findings were collected. The following self-report instruments were used: General Health Questionnaire (GHQ-28) and Defense Style Questionnaire (DSQ).ResultsThe odds of being assessed with a psychiatric diagnosis upon interview were three times greater among patients with ONFH compared to healthy controls (p < .006). The presence of cerebral WML and secondary nature of ONFH were associated with intense symptoms of psychological distress and especially with somatic symptoms of depression and social dysfunction (p < .003). A specific personality structure was identified in patients with ONFH.ConclusionsPatients suffering from osteonecrosis of femoral head, especially when white matter lesions are present, often present psychological distress and problematic personality organization. Therefore psychological support and/or psychiatric intervention can be beneficial to these individuals.

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Evaluation of Paroxysmal Nocturnal Hemoglobinuria Disease Burden: The Patient's Perspective. A Report From the International PNH Registry.

Blood ◽

10.1182/blood.v116.21.1525.1525 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1525-1525 ◽

Cited By ~ 3

Author(s):

Petra Muus ◽

Jeffrey Szer ◽

Hubert Schrezenmeier ◽

Robert A Brodsky ◽

Monica Bessler ◽

...

Keyword(s):

Abdominal Pain ◽

Chest Pain ◽

Board Of Directors ◽

Disease Burden ◽

Advisory Committees ◽

Clone Size ◽

The Past ◽

Patient Reported ◽

History Of ◽

Equity Ownership

Abstract Abstract 1525 Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal hematopoietic stem cell disease characterized by complement-mediated hemolysis, a variable degree of bone marrow failure and thrombophilia, which may lead to reduced quality of life (QOL). There have been few reports of the disease burden of PNH from the patient's perspective. Aims: To describe patient-reported QOL, hospitalization, and missed work at time of PNH registry enrollment and to evaluate the association of these patient-reported outcomes (PROs) with demographics; patient reported symptoms (abdominal pain, chest pain and hemoglobinuria); and clinical characteristics (years since diagnosis, granulocyte clone size, underlying bone marrow disorder [BMD] and prior thrombotic event [TE]). Methods: Enrollment data from 117 clinical sites participating in the observational PNH Registry in 16 countries on 5 continents was analyzed. Patients are included in the Registry if they have a PNH clone regardless of clone size, other BMD, symptoms, or treatments. As part of the study, patients are asked to complete questionnaires at enrollment including the six subscales of the EORTC QLQ-C30 (range=0-100, higher scores better) and the FACIT-Fatigue scale (range=0-52, higher scores better). Patients are also asked “in the past 6 months have you been admitted to a hospital for your PNH” and “in the past 6 months did you miss work as a result of PNH” (questions about work were added later in the study). Statistical analysis used ANOVA and Chi-square tests as appropriate. Results: As of August 2010 there were 657 patients enrolled in the Registry. Of these, 377 (57%) patients completed a baseline questionnaire (BQ) and are included in this analysis. Patients with and without a completed BQ were comparable on most study variables, although patients with a higher clone size were less likely to complete a BQ. Patients had a mean age of 45.8±17.6 years; 54% were female. Median PNH (granulocyte) clone size was 75% (nearly two-thirds had a clone size ≥50%), 45% had BMD (mostly aplastic anemia) and 12% had history of TE. Abdominal pain in the last 6 months was reported by 45% of patients, chest pain by 28%, and hemoglobinuria by 64%. Mean EORTC scores (general population reference in parenthesis) were: global health=64.4 (71.2), physical functioning=79.7 (89.8), role functioning=73.9 (84.7), emotional functioning=76.0 (76.3), cognitive functioning=81.1 (86.1), and social functioning=77.2 (87.5). Thus, scores for PNH patients were decreased by about 10% in 4 of the 6 subscales. PNH patients had a mean FACIT-Fatigue score of 36.6, while a general population reference is 43.6 (or a 16% reduction). PROs were independent of time since diagnosis, PNH clone size, or underlying BMD. Males reported better physical, emotional, and social functioning and less fatigue than females (all p<.05). As expected, age strongly affected physical functioning (p<.01). Patients with prior TE reported worse global health, physical, role, cognitive functioning, and more fatigue than patients without prior TE (all p<.05). Patients reporting abdominal pain, chest pain, or hemoglobinuria had significantly worse EORTC and FACIT-fatigue scores on every scale (all p<.05). Overall, 26% of patients had a PNH-related hospitalization in the past 6 months. Patients who reported TE, abdominal pain, chest pain, or hemoglobinuria were more likely to be admitted to the hospital (all p<.05). There were 109 patients out of 244 (45%) who worked at a paid job. Of these,30% missed work in the past 6 months due to PNH. Patients were more likely to miss work if they had abdominal pain (47% vs 19%, p<.01 or hemoglobinuria (42% vs. 7%, p<.01). Conclusion: The disease burden to PNH patients is evident. Mean QOL is reduced in patients with PNH by 10 to 16% on most scales compared to the general population. One of four patients was hospitalized and 30% of patients with a paid job missed work due to PNH over a 6-month period. History of thrombosis and presence of PNH-related symptoms strongly affected QOL and hospitalization, while missed work was mostly impacted by symptoms. This global PNH Registry, which remains open to accrual ([email protected]), should help to redefine prospectively the long-term natural history of PNH, its treatments, and the outcomes of treatment, including outcomes measured from the patient's perspective. Disclosures: Muus: Celgene: Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Szer:Alexion Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees. Schrezenmeier:Alexion Pharmaceuticals, Inc: Honoraria, Membership on an entity's Board of Directors or advisory committees. Brodsky:Alexion Pharmaceuticals, Inc: Membership on an entity's Board of Directors or advisory committees. Bessler:Alexion Pharmaceutical Inc: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Taligen: Consultancy. Socié:Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees. Urbano-Ispizua:Alexion: Membership on an entity's Board of Directors or advisory committees. Maciejewski:Celgene: Research Funding; Eisai: Research Funding; Alexion: Consultancy. Rosse:Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees. Kanakura:Alexion: Membership on an entity's Board of Directors or advisory committees. Khursigara:Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. Karnell:Alexion Pharma International: Employment, Equity Ownership. Bedrosian:Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. Hillmen:Alexion Pharmaceuticals, Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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The frequency and characteristics of MS misdiagnosis in patients referred to the multiple sclerosis centre of Catalonia

Multiple Sclerosis Journal ◽

10.1177/1352458520988148 ◽

2021 ◽

pp. 135245852098814 ◽

Cited By ~ 1

Author(s):

Luciana Midaglia ◽

Jaume Sastre-Garriga ◽

Agustín Pappolla ◽

Laura Quibus ◽

René Carvajal ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Low Frequency ◽

White Matter Lesions ◽

Final Diagnosis ◽

Personal History ◽

Contributing Factors ◽

Mri Findings ◽

History Of ◽

A Prospective Study

Background: Multiple sclerosis (MS) misdiagnosis may cause physical and emotional damage to patients. Objectives: The objective of this study is to determine the frequency and characteristics of MS misdiagnosis in patients referred to the Multiple Sclerosis Centre of Catalonia. Methods: We designed a prospective study including all new consecutive patients referred to our centre between July 2017 and June 2018. Instances of misdiagnosis were identified, and referral diagnosis and final diagnosis were compared after 1 year of follow-up. Association of misdiagnosis with magnetic resonance imaging (MRI) findings, presence of comorbidities and family history of autoimmunity were assessed. Results: A total of 354 patients were referred to our centre within the study period, 112 (31.8%) with ‘established MS’. Misdiagnosis was identified in eight out of 112 cases (7.1%). MRI identified multifocal white matter lesions, deemed non-specific or not suggestive of MS in all misdiagnosed cases. Patients with MS misdiagnosis had more comorbidities in general than patients with MS ( p = 0.026) as well as a personal history of autoimmunity ( p < 0.001). Conclusion: A low frequency of MS misdiagnosis was found in our clinical setting. Multifocal non-specific white matter lesions in referral MRI examinations and the presence of comorbidities, including a personal history of autoimmunity, seem to be contributing factors to misdiagnosis.

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Methadone-Induced Encephalopathy: A Case Series and Literature Review

10.21203/rs.2.15789/v3 ◽

2020 ◽

Author(s):

Maryam Haghighi-Morad ◽

Zahra Naseri ◽

Nazila Jamshidi ◽

Hossein Hassanian-Moghaddam ◽

Nasim Zamani ◽

...

Keyword(s):

White Matter ◽

Brain Mri ◽

Case Series ◽

Neurological Deficits ◽

Cerebral White Matter ◽

High Signal ◽

Mri Findings ◽

Caudate Nuclei ◽

Delayed Onset ◽

Signal Abnormality

Abstract Background: Accidental ingestion or consumption of supra-therapeutic doses of methadone can result in neurological sequelae in humans. We aimed to determine the neurological deficits of methadone-poisoned patients admitted to a referral poisoning hospital using brain magnetic resonance (MR) and diffusion weighted (DW) imaging. Methods: In this retrospective study, brain MRIs of the patients admitted to our referral center due to methadone intoxication were reviewed. Methadone intoxication was confirmed based on history, congruent clinical presentation, and confirmatory urine analysis . Each patient had an MRI with Echo planar T1, T2, FLAIR, and DWI and apparent deficient coefficient (ADC) sequences without contrast media. Abnormalities were recorded and categorized based on their anatomic location and sequence. Results: Ten patients with abnormal MRI findings were identified. Eight had acute- and two had delayed-onset encephalopathy. Imaging findings included bilateral confluent or patchy T2 and FLAIR high signal intensity in cerebral white matter, cerebellar involvement, and bilateral occipito-parietal cortex diffusion restriction in DWI. Internal capsule involvement was identified in two patients while abnormality in globus pallidus and head of caudate nuclei were reported in another. Bilateral cerebral symmetrical confluent white matter signal abnormality with sparing of subcortical U-fibers on T2 and FLAIR sequences were observed in both patients with delayed-onset encephalopathy. Conclusions : Acute- and delayed-onset encephalopathies are two rare adverse events detected in methadone-intoxicated patients. Brain MRI findings can be helpful in detection of methadone-induced encephalopathy.

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Ganglioneuroblastoma of the cerebellum: neuroimaging and pathological features of a case

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2007000200029 ◽

2007 ◽

Vol 65 (2A) ◽

pp. 338-340 ◽

Cited By ~ 9

Author(s):

Emerson L. Gasparetto ◽

Sérgio Rosemberg ◽

Hamilton Matushita ◽

Claudia da Costa Leite

Keyword(s):

Case Report ◽

Pediatric Population ◽

The Other ◽

Pathological Features ◽

Pathological Findings ◽

Mri Findings ◽

History Of ◽

Cerebellar Mass ◽

One Year ◽

Immunohistochemical Studies

OBJECTIVE: To report a case of ganglioneuroblastoma of cerebellum, with emphasis to the neuroimaging and pathological findings. CASE REPORT: A one year and eight-month-old girl presented with a two-month history of hypoactivity and tremor in the legs. The MRI showed an enhancing cerebellar mass hypointense on T1 and hyperintense on T2-weighted images. The patient underwent a craniotomy with resection of the lesion. The histological and immunohistochemical studies defined the diagnosis of ganglioneuroblastoma. CONCLUSION: The MRI findings of our case showed no features which could help in the differentiation between ganglioneuroblastoma and the other common types of posterior fossa neoplasms in the pediatric population.

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Case report: migraine with aura in patient with cadasil

Headache Medicine ◽

10.48208/headachemed.2020.supplement.56 ◽

2020 ◽

pp. 56

Author(s):

Bárbara Costa ◽

Felipe Carvalho ◽

Gabriel Kubota ◽

Daniel Andrade ◽

Ida Fortini

Keyword(s):

Migraine With Aura ◽

Small Vessel Disease ◽

Brain Mri ◽

Previous History ◽

Clinical Feature ◽

Mri Findings ◽

Nerve Blocks ◽

Visual Aura ◽

Greater Occipital Nerve ◽

History Of

IntroductionCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most frequent hereditary cause of brain ischemic small vessel disease (1). Migraine with aura (MA) is typically the presenting and most common clinical feature of CADASIL. The estimated prevalence of MA in CADASIL ranges from 20 to 40% (2).Case Report43-year-old woman, with previous history of hypertension, diabetes, and episodic migraine with visual aura, suffered three episodes of hemihyposthesia in 2016, 2017 and 2018 (one on her right and the other two on her left). In the last of these episodes, she reported worsening of the visual acuity of her right eye, and developed chronic migraine. Brain MRI showed extensive areas of confluent T2 hyperintensity in the white matter, as well as in the nucleocapsular and bilateral thalamic regions. In all three episodes the patient was treated with IV or oral corticosteroids and had partial improvement of the symptoms. The patient had familiar history of relatives who had suffered multiple strokes.DiscussionThe diagnosis of multiple sclerosis was firstly considered due to the evolution in clinical attacks and the response to corticotherapy. However, the patient’s family history, MRI findings and previous diagnosis of migraine with visual aurea lead to the suspicion of CADASIL. This diagnosis was ultimately confirmed through genetic testing that showed C> T variation in NOTCH3 gene. Migraine was successfully treated with greater occipital nerve blocks and topiramate.Final CommentCADASIL stroke-like attacks remain a therapeutic challenge. It is possible that corticosteroid treatment may benefit these patients by reducing the inflammatory process that results from blood-brain barrier breakdown. More studies are needed to evaluate the efficacy and safety of corticotherapy in this population.

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Systematic Analysis of Brain MRI Findings in Adaptor Protein Complex 4–Associated Hereditary Spastic Paraplegia

Neurology ◽

10.1212/wnl.0000000000012836 ◽

2021 ◽

pp. 10.1212/WNL.0000000000012836

Author(s):

Darius Ebrahimi-Fakhari ◽

Julian E Alecu ◽

Marvin Ziegler ◽

Gregory Geisel ◽

Catherine Jordan ◽

...

Keyword(s):

White Matter ◽

Corpus Callosum ◽

Brain Development ◽

Hereditary Spastic Paraplegia ◽

Anterior Commissure ◽

Brain Mri ◽

Adaptor Protein ◽

Spastic Paraplegia ◽

Mri Findings

Background and Objectives:AP-4-associated hereditary spastic paraplegia (AP-4-HSP: SPG47, SPG50, SPG51, SPG52) is an emerging cause of childhood-onset hereditary spastic paraplegia and mimic of cerebral palsy. This study aims to define the spectrum of brain MRI findings in AP-4-HSP and to investigate radio-clinical correlations.Methods:A systematic qualitative and quantitative analysis of 107 brain MRI studies from 76 individuals with genetically-confirmed AP-4-HSP and correlation with clinical findings including surrogates of disease severity.Results:We define AP-4-HSP as a disorder of gray and white matter and demonstrate that abnormal myelination is common and that metrics of reduced white matter volume correlate with severity of motor symptoms. We identify a common diagnostic imaging signature consisting of (1) a thin splenium of the corpus callosum, (2) an absent or thin anterior commissure, (3) characteristic signal abnormalities of the forceps minor (“ears of the grizzly sign”), and (4) periventricular white matter abnormalities. The presence of two or more of these findings has a sensitivity of ∼99% for detecting AP-4-HSP, while the combination of all four is found in ∼45% of cases. Compared to other HSP with a thin corpus callosum, the absent anterior commissure appears to be specific to AP-4-HSP. Our analysis further identified a subset of AP-4-HSP patients with polymicrogyria, underscoring the role of AP-4 in early brain development. Of clinical importance, these patients displayed a higher prevalence of seizures and status epilepticus, many at a young age.Discussion:Our findings define the MRI spectrum of AP-4-HSP providing opportunities for early diagnosis, identification of individuals at risk for complications, and a window into the role of the AP-4 complex in brain development and neurodegeneration.

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Abstract T P362: Prevalence and Clinicoradiological Profile of Japanese Patients with Alzheimer Disease Coexisting Multiple Microbleeds

Stroke ◽

10.1161/str.45.suppl_1.tp362 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Ken Ikeda ◽

Takehisa Hirayama ◽

Takanori Takazawa ◽

Testuhito Kiyozuka ◽

Masaru Yanagihashi ◽

...

Keyword(s):

White Matter ◽

Brain Mri ◽

Japanese Patients ◽

Brain Parenchyma ◽

Rapid Progression ◽

Amyloid Angiopathy ◽

Mri Findings ◽

Age Related ◽

Magnetic Resonance Imaging Mri ◽

Severe Degree

Background: Pathological findings of cerebral amyloid angiopathy (CAA) and Alzheimer’s disease (AD) coexist frequently. Both diseases are associated with β-amyloid deposition and dementia. We aimed to evaluate frequency and clinicoradiological profile of AD patients with multiple microbleeds (MBs) Methods: We reviewed clinical charts and magnetic resonance imaging (MRI) findings in patients with probable AD from 2009 to 2012, according to the DSM-IV. Brain MRI was performed at 1.5 T using protocols, including T2*-weighted gradient-echo or susceptibility-weighted imaging. MBs were defined as rounded, hypointense foci ≤ 10 mm in size in the brain parenchyma. MBs topography was divided into the lobar (L) and the deep/infratentorial (D/I) region. Multiple MBs were defined as the number ≥ 8 in the L or the D/I territory. White matter hyperintensities (WMH) were assessed using the age-related white matter changes scale. Clinicoradiological findings were examined for ≥ 1 year. Prevalence and clinicoradiological profiles were studied in patients with multiple L MBs or multiple D/I MBs. Results: Five hundred fifty patients (238 men and 312 women) were participated in the present study. Mean age (SD) was 78.4 (7.7) years, 78.3 (8.1) in men and 78.6 (7.5) in woman. A total of 132 patients (55 men and 78 women) had at least MB. Prevalence of total MBs was 24.0%, 23.1 in men and 25.0 in women. Multiple L MBs existed in 49 patients (8.9%), 15 men (6.3) and 34 women (10.9). Multiple D/I MBs were found in 44 patients (8.0%), 23 men (9.7) and 21 women (6.7). Clinical profiles of multiple L MBs revealed sudden deterioration, rapid progression, non-hypertension, higher rates of symptomatic subcortical hemorrhage and onset of CAA-associated leukoencephalopathy. Radiological hallmarks exhibited increased number and size of MBs, high score of WMH and asymptomatic subcortical hemorrhage. Clinicoradiological features of multiple D/I MBs exhibited higher rates of hypertension and variable degrees of WMH. Conclusions: The present study indicated that prevalence of multiple MBs was 16.9% in Japanese patients with AD. The clinicoradiological profile suggested severe degree of CAA in patients with multiple L MBs (8.9%) and hypertensive changes in patients with multiple D/I MBs (8.0%).

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