Neurocase最新文献

Alzheimer's disease (AD) is the leading cause of cognitive decline, whereas primary familial brain calcification (PFBC) is rare. We analyzed the clinical and radiological findings of a 75-year-old man who presented with memory impairment. Brain imaging revealed bilateral basal ganglia calcification, severe white matter hyperintensities, and significant amyloid deposition. Genetic analysis identified a heterozygous c.1711 G > A variant in SLC20A2 and a heterozygous c.166 G > A variant in PSEN2. The patient was diagnosed with genetically confirmed PFBC due to a likely pathogenic SLC20A2 variant, together with AD biology. The PSEN2 variant was classified as a variant of uncertain significance.

This study centers on a 44-year-old right-handed Japanese male with moderate Broca's aphasia. During a confrontation-naming task (CNT) during therapy, the person expressed that it was "easier to speak when I recall (in my mind) the Kana (Hiragana and Katakana) characters." To investigate this claim and its relationship to language impairment, this study sought to determine the effect of character type on the CNT, focusing on the person's perceived difference between Kanji and Katakana. We selected pictures corresponding to highly orthographically plausible Kanji and Katakana (more appropriate for comparison than Hiragana) words for CNT and oral reading tasks that the patient performed. The results revealed more correct responses in CNT in the Katakana stimulus group than in the Kanji one; the latency in oral reading was shorter in the Katakana group as well. The results suggest that words written in Katakana have a better naming performance than those in Kanji because of the influence of the characters as represented in the mental imagery of Katakana. A possible reason for this is that, for our respondent, Katakana is more likely to activate phonological information than Kanji. Additionally, the writing and reading training for confrontation-naming may have implicitly influenced the tasks.

Corticobasal syndrome (CBS) is a rare neurodegenerative disorder characterized by asymmetric motor symptoms, cognitive impairment, and cortical dysfunction. While CCNF gene mutations have been reported in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), their role in CBS spectrum remains unexplored. This study aimed to investigate a 48-year-old patient of South Asian origin, presenting with progressive cognitive decline, behavioral disturbances, and asymmetric motor symptoms characteristic of overlap CBS syndrome. Detailed cognitive and behavioral assessments were conducted, along with brain imaging and whole-exome sequencing. Structural modeling was performed to assess the functional impact of the novel CCNF variant. The family history indicated an autosomal dominant inheritance pattern of progressive cognitive decline, further suggesting genetic predisposition. Brain imaging revealed asymmetric atrophy and hypometabolism in the left temporoparietal and prefrontal regions. Genetic analysis identified a novel heterozygous missense variant (p.Met394Leu) in the CCNF gene. Structural modeling and in-silico prediction tools suggested deleterious effects, though its functional significance remains uncertain. The study reports a potential link between CCNF variants and CBS in a South Asian family, expanding the genetic spectrum of overlap CBS. While the findings suggest potential pathogenicity, further research is required to confirm this association and elucidate the underlying mechanisms.

We summarize and review the clinical and genetic characteristics of four adolescents with Hyperhomocysteinemia. Four cases of adolescent-onset Hyperhomocysteinemia diagnosed at Qingdao University Affiliated Hospital were selected as research subjects. Clinical data, whole exome sequencing and Sanger sequencing information of the patients were collected, and gene variation analysis and literature review were conducted. The pathogenic variants carried by the four patients were MAT1A c.895C>T(p.Arg299Cys), CBS c.374G>A(p.Arg125Glu), CBS c.785C>T(p.Thr262Met), and MMACHC c.482G>A(p.Arg161Glu) and c.658_660del(p.Lys220del) along with other site mutations. There were three cases with epileptic seizures as initial manifestation, three cases with varying degrees of intellectual disability, two cases with lens dislocation, one case with cervical artery occlusion leading to cerebral infarction, and one case with extensive white matter lesions. Four patients showed relief of symptoms after treatment with vitamin B and necessary antiepileptic drugs. We combined the cases and relevant literature to retrospectively analyze the characteristics and treatment related to the disease. The onset of Hyperhomocysteinemia in adolescents is early, and the clinical manifestations are broad and atypical. At the same time, it has a significant impact on the growth and development of adolescents and can affect future life for a long time. Early detection and diagnosis have an important impact on prognosis.

Postoperative aphasia is a significant complication following brain tumor resection, affecting both quality of life and prognosis. Currently, speech language therapy (SLT) is the primary approach for treating aphasia, with no alternative rehabilitation options available. However, rTMS has shown promise intreating stroke-related language impairments. In this case report, we applied bilateral rTMS to address aphasia following brain tumor resection. A 36-year-old man with a known diagnosis of an oligodendroglioma (WHO3°) at the temporo-parieto-occipital junction presented with initial mild aphasia. Preoperative diagnostics revealed language-relevant areas in the supramarginal gyrus and infiltration of the AF, ILF and IFOF, leading to the decision to perform an awake craniotomy fortumor resection. Following complete resection, ischemia medial to the resection cavity was observed, resulting in a worsening of aphasia (AAT score_postop196/440). Over 7 days, continuous bilateral rTMS combined with SLT was administered without any severe side effects. The patient's aphasia significantly improved post-treatment (AAT score_Discharge291/440; AAT score_1 Month343/440; AAT score_3 Months 386/440). Given the encouraging results, a potential beneficial effect of the additional rTMS therapy may be suggested. However, larger cohorts and randomized controlled trials are necessary to confirm these preliminary results.

A 63-year-old woman presented with gait disturbance, progressive hearing loss, and sensory dominant polyneuropathy. Brain MRI mainly revealed midbrain tegmental atrophy (hummingbird sign). Genetic testing identified a heterozygous DNMT1 exon 21 mutation, previously linked to autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN), although her clinical presentation resembled hereditary sensory and autonomic neuropathy type 1E (HSAN1E). A review of previously published cases with the same mutation revealed variability in sensory involvement, cerebellar signs, and sleep disorders, supporting the existence of a wide disease spectrum of DNMT1-related disorders. This case illustrates the phenotypic and radiological overlap within DNMT1-related disorders and supports the concept of a disease spectrum, rather than discrete syndromes, highlighting the diagnostic value of combining neuroimaging with genetic analysis.

Background: VPS13D-related disorders are autosomal recessive genetic disorders characterized by movement disorders primarily including ataxia and spasticity, mainly accompanying developmental delay, seizures, and neuroimaging abnormalities. VPS13D-related spectrum disorder (VSD) may better reflect the characteristics of the disease. So far, the relationship of VPS13D genotype and phenotype of VSD has not been established.

Methods: We analyzed clinical data and collected DNA samples from a severe patient and his healthy parents. Whole exome sequencing was performed by next-generation sequencing. We presented a review of all cases with VSD to establish genotype-phenotype correlation.

Results: The patient had compound heterozygous mutations (c.9785T>C, p.L3262P; c.8687C>T, p.T2896M) in VPS13D gene, maternally and paternally inherited, respectively. The p.L3262P is a novel mutation. The individual presented with ataxia, dystonia, developmental delay, epilepsy and neuroimaging abnormalities, including bilateral caudate and putamen, cerebellum, and right temporal lobe, which are the first detailed imaging study reported in VSD to date. We first report that the patient has achieved significant improvement through active treatment. We first summarize genotype-phenotype correlation of VSD, highlighting that the severity of the phenotype is mainly due to the mutations affecting important domains of VPS13D protein or special severe missense mutations.

Conclusions: Neuroimaging analysis is helpful to the etiology study of VSD. Active treatment of VSD is still meaningful. Important VPS13D regions correlated with severe phenotype need to be further studied.

Variants in VCP (encoding valosin-containing protein) lead to inclusion body myopathy, which is typically associated with Paget's disease of the bones and frontotemporal dementia (FTD). When symptoms of frontotemporal lobar degeneration (FTLD) develop in patients with pathogenic VCP variants, the symptoms mainly present as behavioral-variant (bv) FTD and rarely as semantic dementia (SD). Various pathogenic VCP variants have been reported to cause bvFTD, whereas the only variant previously linked to SD is VCP p.Arg155Cys. Here, we report the case of a female Japanese patient with SD carrying the pathogenic VCP variant p.Arg191Gln. The patient developed naming difficulties, word-finding difficulties, stereotypical behavior, decreased spontaneity, and executive dysfunction at 55 years old and was diagnosed with SD at our hospital at 56 years old. At 59 years, there were no clinical findings suggestive of myopathy, pyramidal signs, or bone involvement. Genetic analyses, including whole-exome and Sanger sequencing, identified the VCP p.Arg191Gln variant in the patient with isolated SD. She required wheelchair assistance for 62 years and was mute. She later died from complications of malnutrition due to feeding difficulties. This case suggests that VCP variants may result in not only bvFTD but also SD, indicating a broader spectrum of FTLD-related phenotypes linked to pathogenic VCP variants.

Dentatorubral-Pallidoluysian Atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disorder caused by CAG repeat expansion in the ATN1 gene, characterized by diverse neurological and psychiatric symptoms. We report a 23-year-old patient with juvenile-onset seizures, cognitive decline, and ataxia, progressing to psychosis by age 31. Initial brain MRI showed minimal cerebellar atrophy, with prominent atrophy evident on follow-up imaging. Genetic testing confirmed DRPLA with expanded CAG repeats. Family history revealed anticipation, with varying presentations across generations. This case highlights DRPLA's complexity, diagnostic challenges due to symptom overlap, and the critical role of genetic testing in identifying this rare disorder.

Fahr's disease (FD) is a rare neurological disorder that causes abnormal, symmetrical, and bilateral calcification of the basal ganglia and other brain regions. Psychiatric symptoms are one of the many manifestations that guide FD diagnosis, with most usually occurring by ages 30-60 years. Herein, we report an incidental finding of bilateral basal ganglia calcification in a 14-year-old male teenager presenting psychotic characteristics, including schizophreniform and manic-like symptoms, who was initially investigated for mycoplasma infection. No similar study has been reported so far in the literature. Case report and literature review. Computed tomography (CT) revealed a calcification deposit in bilateral basal ganglia, thalamus, frontal cortex, and semioval center, magnetic resonance imaging detected a T1-weighted image and fluid-attenuated inversion recovery hyperintense signal abnormalities in the bilateral basal ganglia and thalami. Furthermore, the laboratory tests revealed no obvious abnormality except for hypocalcemia and low vitamin D levels with an elevated uric acid level. The gene test results confirmed the diagnosis of familial FD, which was caused by a mutation in the SLC20A2 gene (NM_001257180.2:c.551delC/p.Pro184Glnfs *8). The patient was prescribed oral medication, including olanzapine, sodium valproate extended-release tablets, lorazepam, and vitamin D drops. Additionally, individualized administration with therapeutic drug monitoring was recommended for the patient to enable dose adjustments. The patient experienced no new psychotic symptoms within the 6-month follow-up after discharge. Bilateral basal ganglia calcification may be a contributing factor to the sudden onset of psychiatric symptoms in children and adolescents.