Clinical comparative analysis of monophasic and multiphasic acute disseminated encephalomyelitis in adults.

Introduction: This study aims to explore the clinical features and prognostic factors for relapse of acute disseminated encephalomyelitis (ADEM) in adults. Material and methods: 56 patients with ADEM were retrospectively analyzed. The epidemiological characteristics, clinical manifestations, laboratory features, magnetic resonance imaging (MRI), treatment and prognosis data of these patients were analyzed using the χ2 test for categorical variables and Mann-Whitney U-test for continuous variables. Then, the clinical characteristics and recurrence factors were summarized. Results: 56 patients with ADEM, based on the criteria of the International Pediatric Multiple Sclerosis Study Group, were recruited to the study. Among these patients, 31 were male and 25 were female. Furthermore, 13 patients had multiphasic ADEM, and 29 patients (52%) had definite incentive factors before onset. The commonest presenting symptoms and signs were fever (36%), disturbance of consciousness (52%), mental disorder (38%), seizure (14%), headache and dizziness (43%), optic neuritis (34%), autonomic nervous system symptoms (43%), limb paralysis or abnormal sensation (73%), and unilateral or bilateral pyramidal tract signs (48%). Inflammatory changes in the cerebrospinal fluid were prominent. MRI T2-weighted and fluid-attenuated inversion recovery images displayed multiple or large flaky high signals, and the lesions were usually different in the number and distribution of these lesions. Intravenous corticosteroids and/or immunoglobulin were still important treatments in the acute phase. After treatment, 38 patients completely recovered, 9 patients had neurologic deficits, and 9 patients died. Conclusions: ADEM in adults is not uncommon, its clinical features are complex and varied, and some of these are multiphasic. There may be some potential clinical predictors at first onset.

The severity of corneal nerve loss differentiates motor subtypes in patients with Parkinson's disease.

Background: Parkinson's disease (PD) is a heterogeneous movement disorder with patients manifesting with either tremor-dominant (TD) or postural instability and gait disturbance (PIGD) motor subtypes. Small nerve fiber damage occurs in patients with PD and may predict motor progression, but it is not known whether it differs between patients with different motor subtypes. Objective: The aim of this study was to explore whether there was an association between the extent of corneal nerve loss and different motor subtypes. Methods: Patients with PD classified as TD, PIGD, or mixed subtype underwent detailed clinical and neurological evaluation and corneal confocal microscopy (CCM). Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL) were compared between groups, and the association between corneal nerve fiber loss and motor subtypes was investigated. Results: Of the 73 patients studied, 29 (40%) had TD, 34 (46%) had PIGD, and 10 (14%) had a mixed subtype. CNFD (no./mm2, 24.09 ± 4.58 versus 28.66 ± 4.27; p < 0.001), CNBD (no./mm2, 28.22 ± 11.11 versus 37.37 ± 12.76; p = 0.015), and CNFL (mm/mm2, 13.11 ± 2.79 versus 16.17 ± 2.37; p < 0.001) were significantly lower in the PIGD group compared with the TD group. Multivariate logistic regression showed that higher CNFD (OR = 1.265, p = 0.019) and CNFL (OR = 1.7060, p = 0.003) were significantly associated with the TD motor subtype. The receiver operating characteristic (ROC) analysis demonstrated that combined corneal nerve metrics showed excellent discrimination between TD and PIGD, with an area under the curve (AUC) of 0.832. Conclusion: Greater corneal nerve loss occurs in patients with PIGD compared with TD, and patients with a higher CNFD or CNFL were more likely to have the TD subtype. CCM may have clinical utility in differentiating different motor subtypes in PD.

Complex cerebrovascular diseases in Roberts syndrome caused by novel biallelic ESCO2 variations.

OBJECTIVE: Roberts syndrome (RBS), also known as Roberts-SC phocomelia syndrome, is a rare autosomal recessive developmental disorder caused by mutations in the ESCO2 gene. Cardinal clinical manifestations are pre- and postnatal growth retardation and craniofacial and limb malformations. Here, we report RBS in a Chinese adolescent with novel biallelic ESCO2 variations and complex cerebrovascular diseases. METHODS: Medical history, neurological examinations, neuroimaging, and pathology were collected in the proband and the family. Whole exome sequencing (WES) with copy number variation analysis was performed to screen for genetic variations. RESULTS: The clinical features of the proband were craniofacial and limb malformations together with complex cerebrovascular diseases. She suffered ischemic stroke at 6 years old and died of cerebellar hemorrhage secondary to an aneurysm at 13 years old. Besides, neuroimaging showed the triad of leukoencephalopathy, calcifications, and cysts. Brain histopathology revealed angiomatous changes and perivascular cysts suggesting chronic small cerebral vasculopathy. Whole exome sequencing (WES) identified novel biallelic variations in the ESCO2 gene (c.1220A>T, p.H407L and c.1562delC, p.A521fs). CONCLUSIONS: We describe complex cerebrovascular diseases in Roberts syndrome caused by novel ESCO2 biallelic variations. This case expands not only the cerebral involvement in Roberts syndrome but also the disease spectrum of the neuroimaging triad with leukoencephalopathy, calcifications, and cysts.

Adult-onset autosomal dominant leukodystrophy and neuronal intranuclear inclusion disease: lessons from two new Chinese families.

INTRODUCTION: Adult-onset autosomal dominant leukodystrophy (ADLD) is a rare genetic leukoencephalopathy caused by duplication of the lamin B1 gene (LMNB1) or LMNB1 upstream deletions. Neuronal intranuclear inclusion disease (NIID) is another leukoencephalopathy due to GGC repeat expansion in the 5'-untranslated region of the NOTCH2NLC gene. Here, we report two Chinese ADLD families with neuroimaging and clinical features mimicking NIID. METHODS: We conducted detailed medical history inquiry, neurological examinations, and magnetic resonance imaging in the two families. Candidate gene sequencing and whole exome sequencing (WES) with copy number variation analysis were used to screen the genetic variations. The special points on the clinical and neuroimaging findings in the current families and differential diagnosis of ADLD with NIID are discussed. RESULTS: The two families presented with slowly progressive, multiple central nervous system symptoms, including spastic paraplegia, autonomic dysfunction, ataxia, deep sensory loss, and tremor. Clinical phenotypes were consistent within the family. Transient hypoglycemia and transient dilated pupils indicating autonomic dysfunctions were recorded for the first time in ADLD. Brain MRI showed band-like hyperintensities at the cortico-medullary junction on DWI, typical for NIID. Skin biopsy and genetic sequencing of the NOTCH2NCL gene did not support the diagnosis of NIID. Further whole exome sequencing (WES) identified the duplication mutation spanning the entire LMNB1 gene. CONCLUSIONS: The novel feature of transient hypoglycemia and dilated pupils broadens the spectrum of autonomic dysfunction in ADLD. Clinical manifestations and neuroimaging of ADLD can mimic NIID. Although ADLD is even rarer than NIID, the differential diagnosis of these two diseases should not be confused.

Comparative Study on Topological Properties of the Whole-Brain Functional Connectome in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinson's Disease Without RBD.

Purpose: Idiopathic rapid eye movement Sleep Behavior Disorder (iRBD) is considered as a prodromal and most valuable warning symptom for Parkinson's disease (PD). Although iRBD and PD without RBD (nRBD-PD) are both α-synucleinopathies, whether they share the same neurodegeneration process is not clear enough. In this study, the pattern and extent of neurodegeneration were investigated and compared between early-stage nRBD-PD and iRBD from the perspective of whole-brain functional network changes. Methods: Twenty-one patients with iRBD, 23 patients with early-stage nRBD-PD, and 22 matched healthy controls (HCs) were enrolled. Functional networks were constructed using resting-state functional MRI (fMRI) data. Network topological properties were analyzed and compared among groups by graph theory approaches. Correlation analyses were performed between network topological properties and cognition in the iRBD and nRBD-PD groups. Results: Both patients with iRBD and patients with early-stage nRBD-PD had attention, executive function, and some memory deficits. On global topological organization, iRBD and nRBD-PD groups still presented small-worldness, but both groups exhibited decreased global/local efficiency and increased characteristic path length. On regional topological organization, compared with HC, nRBD-PD presented decreased nodal efficiency, decreased degree centrality, and increased nodal shortest path length, while iRBD presented decreased nodal efficiency and nodal shortest path. For iRBD, brain regions with decreased nodal efficiency were included in the corresponding regions of nRBD-PD. Nodal shortest path changes were significantly different in terms of brain regions and directions between nRBD-PD and iRBD. Attention deficits were correlated with local topological properties of the occipital lobe in both iRBD and nRBD-PD groups. Conclusion: Both global and local efficiency of functional networks declined in nRBD-PD and iRBD groups. The overlaps and differences in local topological properties between nRBD-PD and iRBD indicate that iRBD not only shares functional changes of PD but also presents distinct features.

Encephalitis in Kikuchi-Fujimoto disease being immune-mediated.

INTRODUCTION: Histiocytic necrotizing lymphadenitis, also known as Kikuchi-Fujimoto disease, is a rare benign self-limiting inflammatory disease often seen in young adults. The main clinical features are fever with cervical lymphadenopathy. Neurological complications of Kikuchi-Fujimoto disease were occasionally reported although the specific pathogenesis was not clear. The condition could be severe when encephalitis coexists. METHODS: Here we reported a young case of Kikuchi-Fujimoto disease with subsequent severe autoimmune encephalitis. RESULTS: The symmetric striatal and limbic MRI lesions combined with psycho-cognitive, epileptic symptoms supported encephalitis. Tissue-based immunofluorescence revealed widely cytoplasmic fluorescence in rat cerebellar and hippocampal neurons, which provide evidence for immune-mediated encephalitis. The clinical outcome was satisfactory after immunosuppressive therapy with MRI lesions largely disappeared. CONCLUSION: The encephalitis complication of Kikuchi disease may be autoimmune and mediated by cytotoxic T cells.

Novel Mutation of Hydroxymethylbilane Synthase in a Case of Acute Intermittent Porphyria Presenting with Posterior Reversible Encephalopathy Syndrome.

Acute intermittent porphyria (AIP) is an autosomal, dominant, hereditary metabolic disease caused by an inherited deficiency of hydroxymethylbilane synthase (HMBS), a crucial enzyme in the heme biosynthetic pathway. It can affect the central, peripheral, and autonomic nervous systems. We report a 23-year Chinese woman who presented with severe abdominal pain, convulsions, constipation, tachycardia, quadriparesis, and hyponatremia, accompanied by posterior reversible encephalopathy syndrome (PRES). The clinical diagnosis of AIP was made after positive urine Watson-Schwartz test for porphobilinogen (PBG). Genetic testing is important for AIP patients in confirming the diagnosis. We identified a new insertion mutation in intron 14 [c.1005dupC (p.I336Hfs*23)] of the HMBS in her genomic DNA. Timely and accurate treatment of AIP may improve disease prognosis. Key Words: Acute intermittent porphyria, Mutation, Posterior reversible encephalopathy syndrome.

More autosomal dominant SPG18 cases than recessive? The first AD-SPG18 pedigree in Chinese and literature review.

OBJECTIVE: Hereditary spastic paraplegia (HSP) due to ERLIN2 gene mutations was designated as spastic paraplegia 18 (SPG18). To date, SPG18 families/cases are still rarely reported. All early reported cases shared the autosomal recessive (AR) inheritance pattern. Over the past 3 years, autosomal dominant (AD) or sporadic SPG18 cases had been continuously reported. Here, we reported the clinical and genetic features of the first autosomal dominant SPG18 pedigree in Chinese. METHODS: We conducted detailed medical history inquiry, neurological examinations of the proband and his family members, and charted the family tree. The proband underwent brain and cervical magnetic resonance imaging (MRI), electromyography (EMG), and whole exome sequencing. Sanger sequencing was performed to verify the genetic variation in the proband and some family members. A literature review of all reported SPG18 families/cases was carried out to summarize the clinical-genetic characteristics of SPG18 under different inheritance patterns. RESULTS: Four patients were clinically diagnosed as chronic spastic paraplegia in three consecutive generations with the autosomal dominant inheritance model. All the patients presented juvenile-adolescent onset and gradually worsening pure HSP phenotype. Clinical phenotypes were consistent within the family. Whole exome sequencing in the proband identified a previously reported heterozygous c.502G > A (p.V168M) mutation in exon 8 of ERLIN2 gene. This mutation was cosegregated with the phenotype in the family and was classified as likely pathogenic according to American College of Medical Genetics and Genomics (ACMG) guidelines. To date, eight AR-SPG18 families, five AD-SPG18 families, and three sporadic cases had been reported. Clinical phenotype of AD-SPG18 was juvenile-adolescent onset pure HSP, while the phenotype of AR-SPG18 was mostly complicated HSP with earlier onset and more severe conditions. In rare cases, the initial spastic paraplegia could evolve to rapidly progressive amyotrophic lateral sclerosis (ALS). CONCLUSIONS: We reported the first autosomal dominant SPG18 pedigree in Chinese Han population, which added more pathogenic evidence for V168M mutation. As more SPG18 cases reported, the essentials of SPG18 need to be updated in clinical practice. Special attentions should be given in gene test for upper motor neuron disorders in case of missing heterozygous mutations in ERLIN2.

Isolated Enhancement Effect is the Only MRI Finding for Wernicke's encephalopathy.

Wernicke's encephalopathy (WE) is an acute neuropsychiatric disorder that results from thiamine (vitamin B1) deficiency. The typical clinical manifestations, which occur as triads in 20% of patients with the disorder, are acute mental status changes, ophthalmoplegia, and ataxia. Brain magnetic resonance imaging (MRI) has important value in diagnosis as it can reveal abnormalities in the thalamus, mammillary body, third and fourth ventricles, and periaqueductal area. Here we describe a 44-year-old female patient with WE, in the context of fasting following bowel surgery. The unique neuroimaging findings were symmetrical mammillary body and dorsal midbrain abnormalities, only evident on contrast-enhanced brain MRI.

Abnormal Striatal-Cortical Networks Contribute to the Attention/Executive Function Deficits in Idiopathic REM Sleep Behavior Disorder: A Resting State Functional MRI Study.

INTRODUCTION: The structural and functional damages of the striatum were evident in idiopathic REM sleep behavior disorder (iRBD). With the research on iRBD deepens, cognitive impairment in iRBD is getting increasing attention. However, the mechanism of cognitive impairment in iRBD was poorly understood. METHODS: Neuropsychological assessment was carried out in 21 polysomnographies (PSGs) confirmed iRBD patients and 22 normal controls. Both regional homogeneity (ReHo) and seed-based functional connectivity (FC) rs-fMRI analyses were applied to explore the FC abnormalities and its association with cognition in iRBD patients. Positive ReHo clusters were set as seeds for further FC analysis. RESULTS: Idiopathic REM sleep behavior disorder patients presented cognitive deficits in attention/working memory, executive function, immediate memory, and visuo-spatial ability. ReHo analysis revealed abnormal spontaneous brain activities in the striatum (right caudate, left pallidum and bilateral putamen) in iRBD. FC analysis showed decreased striatum-related FCs in the frontal, temporal, occipital lobes, thalamus, anterior cingulate gyrus, as well as decreased intrinsic FCs between bilateral putamen and between caudate and pallidum. Deficits in attention/working memory, executive function, and immediate memory were associated with abnormal striatal-cortical FCs including frontal, temporal, and anterior cingulate cortices. CONCLUSION: Functional changes of striatum and cognitive impairment in iRBD were reconfirmed in the present study. Abnormal striatal-cortical networks, especially the striatal-frontal network, contribute to the working memory/executive function deficits in iRBDs. These findings supported the role of striatum not only in motor but also in cognition impairment in iRBD.

Genome-wide CRISPR/Cas9 screening identifies CARHSP1 responsible for radiation resistance in glioblastoma.

Glioblastomas (GBM) is the most common primary malignant brain tumor, and radiotherapy plays a critical role in its therapeutic management. Unfortunately, the development of radioresistance is universal. Here, we identified calcium-regulated heat-stable protein 1 (CARHSP1) as a critical driver for radioresistance utilizing genome-wide CRISPR activation screening. This is a protein with a cold-shock domain (CSD)-containing that is highly similar to cold-shock proteins. CARHSP1 mRNA level was upregulated in irradiation-resistant GBM cells and knockdown of CARHSP1 sensitized GBM cells to radiotherapy. The high expression of CARHSP1 upon radiation might mediate radioresistance by activating the inflammatory signaling pathway. More importantly, patients with high levels of CARHSP1 had poorer survival when treated with radiotherapy. Collectively, our findings suggested that targeting the CARHSP1/TNF-α inflammatory signaling activation induced by radiotherapy might directly affect radioresistance and present an attractive therapeutic target for GBM, particularly for patients with high levels of CARHSP1.

Behavioral and neurobiological changes in a novel mouse model of schizophrenia induced by the combination of cuprizone and MK-801.

Schizophrenia is a mental illness characterized by episodes of psychosis, apathy, social withdrawal, and cognitive impairment. White matter lesions and glutamatergic hypofunction are reported to be the key pathogeneses underlying the multiple clinical symptoms of schizophrenia. Cuprizone (CPZ) is a copper chelator that selectively injures oligodendrocytes, and MK-801 is an antagonist of the N-methyl d-aspartate (NMDA) receptor. To better mimic the psychosis and complicated pathogenesis of schizophrenia, a novel possible mouse model was established by the combination of CPZ and MK-801. After exposure to CPZ for 5 weeks, the mice received a daily intraperitoneal injection of MK-801 for 2-weeks. Behavioral changes in the mouse model were evaluated using Y-maze, object recognition, and open field tests. Pathological changes were observed by transmission electron microscopy, oil red O staining, immunohistochemistry, and western blotting. The results showed that the novel mouse model induced by CPZ plus MK-801 exhibited severe spatial and recognition memory deficits, hyperactivity, and anxiety disorder. Moreover, the mice showed obvious demyelination and white matter damage and decreased expression levels of myelin basic protein (MBP) and 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) in the corpus callosum. Furthermore, the phosphorylation levels of Fyn and NMDA receptor 2B in the corpus callosum and NMDA receptor 1 in the cerebral cortex were noticeably decreased. Taken together, the novel mouse model induced by the combination of cuprizone and MK-801 showed comprehensive behavioral and neurobiological changes, which might make it a suitable animal model for schizophrenia.

Watch out for neuromyelitis optica spectrum disorder after inactivated virus vaccination for COVID-19.

With recent availability of COVID-19 vaccine, post-vaccination neurological complications had been occasionally reported. Here, we reported for the first time a case of neuromyelitis optica spectrum disorder (NMOSD) that developed after the first dose of inactivated virus vaccine for COVID-19. The patient developed mild fever, vomiting, diarrhea, and cough after receiving the first dose of inactivated virus vaccine. Two months later, she experienced dizziness and unsteady walking. MRI scanning of the brain revealed lesions in area postrema and bilateral hypothalamus, typical for NMOSD. Serum antibodies for AQP4, ANA, SSA, SSB, Ro-52, and p-ANCA were positive. The patient was diagnosed as AQP4-positive NMOSD with coexisting systemic autoimmunity. After treatment with methylprednisolone (500 mg for 5 days), symptoms were greatly relieved. As NMOSD is seriously harmful and curative, it is important to be aware of the NMOSD symptoms after vaccination. Cautions should be given for those with preexisting systemic autoimmune abnormalities in vaccination for COVID-19.

Risk Factors for Long-Term Death After Medullary Infarction: A Multicenter Follow-Up Study.

Background and Purpose: We investigated the risk factors for death in patients with medullary infarction (MI) during a long-term follow-up. Methods: We retrospectively examined 179 consecutive patients (130 men and 49 women) who had clinical and MRI findings consistent with MI between February 2012 and January 2017 at three university hospitals. Long-term outcomes were assessed by telephonic interview. The clinical and radiological features and risk factors for poor outcomes (modified Rankin scale score ≥ 3, all-cause death) were analyzed. Results: Mean age of patients was 58.3 ± 12.8 years (range, 25-87); mean follow-up period after stroke onset was 42.7 ± 13.2 months (range, 24-78). Basilar artery (BA) stenosis >50% was more closely related to medial medullary infarction (MMI) than other types. There was greater frequency of ipsilateral vertebral artery hypoplasia (VAH) or V4AH and V4 occlusion in lateral MI than in other types. On rostro-caudal classification, middle (M)+dorsal (D) was most frequent, followed by the ventral (V)+M+D types. 21.2% patients showed poor long-term prognosis. Age ≥ 65 years, recurrent stroke, dysphagia, >50% BA stenosis, and ventral MI were risk factors for poor long-term prognosis. All-cause mortality rate was 10.6%; age ≥ 65 years, recurrent stroke, and dysphagia were risk factors for death in the long-term. Ventral MI and MMI+cerebellar infarction, as well as stroke mechanism of artery-to-artery embolism, were potential risk factors for death in the long-term. Pneumonia and recurrent stroke were major causes of death. Conclusions: Long-term poor outcomes of MI and all-cause mortality were not infrequent. Older age, recurrent stroke, and dysphagia were common risk factors for poor prognosis and death.

Clinical Presentation of Sporadic Creutzfeldt-Jakob Disease in Han-Chinese.

The clinical presentation in Chinese patients with sporadic Creutzfeldt-Jakob disease (sCJD) may be unique due to the big difference in the codon 129 polymorphism of the prion protein gene (PRNP). This study retrospectively reviewed 26 cases of sCJD diagnosed in a single center in recent years. All 26 sCJD patients received brain magnetic resonance imaging scan, cerebrospinal fluid 14-3-3 protein detection, electroencephalogram, and PRNP gene screening. The codon 129 polymorphism were all homozygous MM in 26 sCJD patients. The main onset symptoms of sCJD patients were rapidly progressive dementia, visual impairment, and cerebellar ataxia. At the time of diagnosis, the incidence of myoclonus and akinetic mutism were relatively low (<50%). For auxiliary examinations, the positive rate of the typical magnetic resonance imaging (MRI) abnormalities, cerebrospinal fluid 14-3-3 protein, and electroencephalogram-periodic sharp wave complex was 96%, 64%, and 50%, respectively. As MM genotype is dominant and brain MRI is sensitive, brain MRI seems to play a major role in diagnosis of sCJD in Chinese.

Hierarchical 3D Nanolayered Duplex-Phase Zr with High Strength, Strain Hardening, and Ductility.

Nanolayered, bimetallic composites are receiving increased attention due to an exceptional combination of strength and thermal stability not possible from their coarse-layered counterparts or constituents alone. Yet, due to their 2D planar, unidirectional arrangement, they are highly anisotropic, which results in limited strain hardening and ductility. Therefore, like many high-performance, ultrastrong materials of our time, they succumb to the usual strength-ductility trade-offs. Here we present the formation of a novel hierarchical microstructure, comprised of crystals consisting of 3D nanolayered α/ß-Zr networks. By direct comparison with coarse-layered material of the same chemistry, we show that the unusual hierarchical 3D structure gives rise to high strain hardening, high strength, and high ductility. Using TEM analysis and hysteresis testing, we discovered that the 3D randomly oriented biphase boundaries result in progressively dispersive rather than localized slip with increasing strain. Dislocation activity in the α-Zr lamellae transitions from single slip to multislip and eventually to multimodal slip as strain increases. The diffusive slip-promoting properties of 3D layered networks can potentially invoke simultaneous high strength, strain hardening, and ductility, and reveal a new target in the microstructural design of high performance structural materials.

A Case of Cerebral Amyloid Angiopathy-Related Inflammation With the Rare Apolipoprotein ε2/ε2 Genotype.

Cerebral amyloid angiopathy (CAA)-related inflammation (CAA-RI) is a rare CAA variant characterized by acute or subacute encephalopathy, headache, epilepsy, or focal neurological deficits. Radiologically, CAA-RI presents with widespread white matter lesions on brain magnetic resonance imaging (MRI) in addition to the hemorrhagic imaging features of CAA. Previous studies have found that the apolipoprotein E (ApoE) ε4 allele and ε4/ε4 genotype were over-represented in CAA-RI. The role of the ApoE ε2 allele in CAA-RI, however, is largely unknown, partly due to the rarity of the ε2/ε2 genotype in the general population. The authors report the first case of CAA-RI with the rare ApoE ε2/ε2 genotype. The patient presented with mild clinical symptoms but striking neuroimaging abnormalities. The response to small-dose glucocorticoids was satisfactory. Because ApoE ε2 promotes amyloid ß accumulation and fibrinoid necrosis in the cerebral vasculature, the ε2/ε2 genotype, similar to ε4/ε4, may also be a precipitating factor for CAA-RI. To clarify the role of ApoE ε2 in CAA-RI, studies with large sample sizes investigating whether ε2 is more common in patients with CAA-RI than in those with CAA only are warranted.

The role of MAPT gene in Chinese dementia patients: a P301L pedigree study and brief literature review.

BACKGROUND AND PURPOSE: Frontotemporal dementia (FTD) is the second most common presenile dementia characterized by behavioral changes and language impairment. The diagnosis of FTD relies heavily on neuroimaging, and sometimes on genetic screening. However, the genetic components in Chinese FTD patients remain largely unknown. Only a few FTD cases with established mutations have been reported in China. This study reported the detailed clinical and neuroimaging features in a Chinese behavioral variant FTD family. The role of MAPT gene mutation in Chinese dementia patients was also reviewed. METHODS: By detailed inquiry of all affected individuals in the family, this study summarized the main clinical features of the disease. Four candidate genes (MAPT, PSEN1, PSEN2, and APP) were screened by direct sequencing. Structural magnetic resonance imaging (MRI), functional imaging of cerebral blood flow with arterial spin-labeled MRI (ASL-MRI), and cerebral metabolism with fluorodeoxyglucose positron emission tomography (FDG-PET) were collected in the proband and healthy mutation carriers. RESULTS: By direct sequencing of candidate genes (MAPT, PSEN1, PSEN2, and APP), this study identified the P301L mutation in the MAPT gene in the proband and three unaffected family members. The phenotype of the affected cases was consistent within the pedigree. In this genetically proven behavioral variant FTD (bvFTD) patient, the maps of hypoperfusion on ASL-MRI look fairly similar to the hypometabolism on FDG-PET. The clinical feature for this bvFTD was in line with the hypoperfusion or hypometabolism pattern on functional neuroimagings. The phenotype of P301L in east Asia seems similar to western countries. CONCLUSION: For the inherited FTD patients, ASL-MRI and genetic identification were strongly recommended for the final diagnosis. In case of being underestimated, the role of MAPT gene mutation in Chinese FTD patients warrants further investigation.