Anterior opercular syndrome (Foix-Chavany-Marie syndrome) is characterized by severe dysarthria, impaired voluntary orofacial and pharyngolingual movements, and preserved automatic or emotional movements (automatic-voluntary dissociation). Although classically associated with stroke, its progressive neurodegenerative form is rare and poorly understood. We report two patients to characterize its clinical and neuroanatomical features. The cases were identified retrospectively through review of clinical and neuroimaging records from behavioral neurology centers in the United States and Japan. Both had severe dysarthria and oral-phase dysphagia. Voluntary orofacial movements were markedly impaired, whereas reflexive movements, including coughing and yawning, and emotional movements, including smiling in response to humor, were preserved. Coordination, posture, and gait were initially preserved. Both patients showed predominantly upper motor neuron features without lower motor neuron signs; limb and cranial electromyography was normal in the patient tested. Neuroimaging showed bilateral frontal atrophy and hypometabolism or hypoperfusion involving the anterior operculum. These findings suggest that progressive anterior opercular syndrome may emerge when bilateral opercular regions are affected by neurodegeneration. Recognition of this syndrome may facilitate anticipatory management of dysarthria, dysphagia, and nutritional risk and broaden awareness of speech and orofacial motor syndromes in frontotemporal dementia and related phenotypes.

Diagnosing non-fluent/agrammatic variant primary progressive aphasia (nfvPPA) relies primarily on apraxia of speech (AOS) and agrammatism. However, differentiating phonetic-level (articulatory) from phonemic-level (phonological) impairments remains clinically challenging, especially in advanced stages. We report a 65-year-old Japanese male with nfvPPA who had become virtually speechless (ἀφημί). Leveraging the Kana writing system's one-to-one correspondence to morae, we designed a cross-modal experiment to isolate his underlying deficit. Speech production was evaluated across four conditions: picture naming, Kanji word reading, Kana word reading, and character-by-character Kana reading. Statistical analysis was performed using Fisher's exact test and adjusted residual analysis. Speech intelligibility significantly improved during character-by-character Kana reading compared to other modalities. Residual analysis confirmed that explicit moraic cues markedly reduced error rates. These findings indicate that our approach effectively unmasked superimposed phonemic-level retrieval deficits contributing to speechlessness in nfvPPA. This study highlights the utility of Japanese orthography in disentangling underlying mechanisms and demonstrates that moraic assistance can serve as a potent facilitation strategy in severe cases.

To assess the possibility that individualized duration of donanemab treatment might enable early pausing of therapy, and to explore the possible utility of plasma P-tau[217] as a biomarker for treatment response monitoring in real-time, two unrelated patients with early-stage Alzheimer's disease were treated with donanemab at the Icahn School of Medicine at Mount Sinai. Clinical progress was monitored via medical chart review, including serial brain MRI, amyloid PET scans, and blood-based biomarker assays (Quanterix Simoa® and Fujirebio Lumipulse®). Both patients achieved complete amyloid clearance as judged by amyloid PET prior to their 6th and 9th infusions, which were significantly earlier than the 12-month mark typically recommended for follow-up amyloid assessment. In agreement with the amyloid PET, concurrently measured plasma P-tau[217] levels fell within a low range. Treatment was discontinued for both patients. These patients highlight the possibility of individualized treatment durations for anti-amyloid therapy with donanemab, guided by biomarker response. Early cessation following rapid plaque clearance could reduce healthcare costs and minimize exposure to the risk of amyloid-related imaging abnormalities and the generation of neutralizing antibodies. Plasma P-tau[217] warrants further investigation as a reliable, cost-effective surrogate for PET scans to monitor real-time treatment response and guide the timing of discontinuation.

Delusional infestation (DI) is an uncommon manifestation of psychosis in Parkinson disease (PD), and is often associated with dopaminergic therapy. We describe a 66-year-old woman with PD who developed visual and tactile delusions of a parasitic infestation while receiving dopaminergic medications. Comprehensive neuropsychological testing revealed largely preserved cognitive functioning, with only mild relative weaknesses in processing speed and problem-solving. The patient's symptoms resolved following discontinuation of amantadine, supporting an iatrogenic etiology. Previous case reports have consistently described a link between DI and dopaminergic overstimulation, although DI has been observed across a broad range of cognitive functioning. This case highlights the diagnostic utility of formal neuropsychological assessment and underscores the importance of recognizing DI as a potentially reversible, iatrogenic phenomenon within the spectrum of PD psychosis.

Hereditary spastic paraplegia (HSP) is a group of genetic disorders caused by >80 genes that can be described as either pure or complex forms.We report a case of a patient with a complex form of SPG7 with significant cognitive impairment.A 42-year-old man presented with a 10-year history of dysarthria, 5 years of gait difficulties, and 3 years of cognitive symptoms. Neuropsychological analysis showed deficits involving speed of information processing, mental flexibility, ideational fluency, verbal concept formation, visual working memory, and visual-spatial perception. Next-generation sequencing on whole blood revealed 2 heterozygous pathogenic variants in SPG7 (c. 1049_1077del, p. Pro350Glnfs*36 and c. 1529C>T, p. Ala510Val).There are emerging reports of complex forms of SPG7 presenting with impairments in memory, executive dysfunction, language, visuospatial processing, social functioning, and emotional communication. In this report, we describe a complex SPG7 patient who underwent formal neuropsychological testing to assess cognitive status in depth. This revealed deficits in speed of processing, visuospatial working memory and perception, impaired non-verbal intellect, and overall lack of insight, which have not yet been described in the literature.

Choroid plexus xanthogranulomas are rare, typically incidental intraventricular lesions that infrequently become symptomatic. When symptomatic, they most often present with headache or hydrocephalus, whereas cognitive sequelae and postoperative neuropsychological outcomes remain poorly characterized. A 63-year-old right-handed man with bilateral trigonal intraventricular lesions, larger on the right, presented with headaches and a history of subjective progressive memory complaints. He underwent resection of the right-sided lesion through a right temporoparietal approach. Immediately after surgery, he developed a severe and persistent amnestic-cognitive syndrome with profound inability to retain new information, confabulation, reduced insight, and marked remote-memory disturbance. Neuropsychological evaluation 3 months postoperatively demonstrated severe anterograde impairment in verbal learning and delayed visuospatial recall, together with substantial retrograde memory impairment involving autobiographical episodic recollection, personal semantic memory, and public semantic knowledge. This case suggests that bilateral trigonal xanthogranulomas and their surgical treatment may place distributed memory networks at substantial risk. Because formal preoperative neuropsychological testing and direct review of the original preoperative MRI were unavailable, the relative contributions of preexisting bilateral disease burden and postoperative network disruption cannot be fully separated. The case supports broader baseline cognitive assessment, precise laterality-specific surgical description, and structured postoperative neuropsychological follow-up for lesions near posterior medial and limbic white-matter pathways.

Visuospatial neglect is a common finding associated with lesions in the middle and posterior cerebral artery territories, with a higher incidence in right hemispheric infarctions. In anterior cerebral artery (ACA) infarction, neglect is typically accompanied by motor deficits or manifests as motor neglect. Pure visuospatial neglect without motor involvement in the setting of ACA infarction therefore represents an uncommon clinical presentation. A 62-year-old woman presented with a cognitive decline, including perseverative behavior and disorientation to time. Brain magnetic resonance imaging (MRI) revealed a right medial frontal acute infarction. Neurological examination revealed intact motor function. However, bedside tests and the Seoul Neuropsychological Screening Battery (SNSB) demonstrated severe left-sided visuospatial neglect with domain-specific dissociation: visuospatial attention was severely impaired while verbal attention remained preserved. Diffusion tensor imaging (DTI) tractography revealed severe and preferential disruption of the right cingulum bundle (78% reduction in tract count; asymmetry ratio 0.22) with relative preservation of the superior longitudinal fasciculus (31.8% reduction in tract count) and intact parietal aslant tract. This case demonstrates that motor-sparing ACA infarction can produce severe pure visuospatial neglect, and highlights the importance of careful neuropsychological evaluation and active rehabilitation even in the absence of motor weakness.

Alexander disease (AxD) is a rare progressive astrogliopathy and leukodystrophy caused by heterozygous pathogenic variants in the gene encoding glial fibrillary acidic protein (GFAP). Cognitive problems in AxD have long been recognized, but domain-specific neuropsychological descriptions of adult-onset Alexander disease (AO-AxD) remain sparse. We report a genetically confirmed 53-year-old man with AO-AxD who underwent comprehensive neuropsychological assessment because of progressive cognitive and behavioral complaints. The profile was characterized by deficient verbal episodic memory retrieval and reduced set-shifting efficiency, with relatively preserved recognition memory, language, visuospatial abilities, and most attentional measures. Structural MRI showed characteristic medullary and upper cervical cord involvement but only limited supratentorial white matter abnormalities. To contextualize the case, we reviewed published AO-AxD reports with domain-specific neuropsychological testing. The available literature remains limited and heterogeneous, but suggests that cognitive manifestations in AO-AxD may include retrieval-based memory deficits, executive inefficiency, and visuospatial difficulties. We discuss these findings in relation to white matter dementia, fronto-subcortical and fronto-hippocampal network dysfunction, and potential astrocyte-mediated mechanisms.

Highly Superior Autobiographical Memory (HSAM) is the rare ability to recollect nearly all of one's past personal experiences with great detail and accuracy. When given a date, a person with HSAM can recall verifiable details about what they experienced that day. People with HSAM do not tend to stand out on standard neuropsychological assessments, common laboratory tasks, or other measures that assess intentional forms of memory. Some clues suggest that the superior autobiographical remembering of people with HSAM occurs involuntarily. In a newly identified case of a person with HSAM, we found evidence using the Involuntary Autobiographical Memory Inventory (IAMI) that the person's involuntary memory indeed stands out. This person's past-oriented Involuntary Autobiographical Memory (IAM) frequency was two standard deviations above the mean reported in previous research. while, in line with past research, her performance on standard neuropsychological batteries and laboratory tasks was unremarkable. We propose that these intrusive recollections facilitate the consolidation of memory for past events.

Posterior Cortical Atrophy (PCA) is a neurodegenerative syndrome defined by occipital atrophy that results in visuospatial deficits, often caused by Alzheimer's disease (AD) pathology. Patients with PCA are younger than typical AD patients and can present with anxiety. A rare and atypical variant of AD, the variable presentation of PCA has left it understudied, misdiagnosed, and with few in-depth examinations of cognitive profiles. This project reviews three patients referred for neuropsychological evaluation who were determined to have probable PCA. A comprehensive neuropsychological battery examined learning and memory, executive function, language, attention and processing speed, and visuospatial ability. Cases were examined based on cognitive complaints, daily functioning based on informant report, neuropsychological test performance, and neurodiagnostic work-up. Striking visuospatial deficits were observed in visuospatial construction tests (all patients scored < 1 percentile), and performance was impaired on most tests with visual components. Memory scores were impaired on some tests, but scores were slightly better on a contextualized verbal task compared to a word list. Patients had trouble functioning related to vision (e.g. object finding, reading) and tested positive for AD biomarkers. These cases highlight key aspects of the neuropsychological work-up for suspected PCA, including visuospatial deficits, AD biomarkers, and cognitive complaints.

Neuronal ceroid lipofuscinoses (NCLs) are rare, genetically heterogeneous neurodegenerative disorders involving progressive cognitive, motor, and psychiatric decline. Adult-onset CLN6 disease (Kufs type) is extremely uncommon, typically emerging after age 30 with seizures, ataxia, and gradual functional deterioration. We report a Chinese brother - sister pair carrying identical compound heterozygous CLN6 mutations (c.307C >T [p.Arg103Trp] and c.425A >G [p.Tyr142Cys]) who exhibited marked intrafamilial phenotypic divergence. The younger sister developed generalized seizures at age 30, followed by focal seizures, gait instability, and progressive ataxia, but remained partially mobile and free of psychiatric symptoms for more than 10 years. By contrast, her older brother developed seizures at age 35 and prominent psychosis at age 42, including persecutory delusions and hallucinations, followed by rapid neurological deterioration and complete dependence within 2 years. This sibship illustrates substantial clinical heterogeneity despite an identical CLN6 genotype. Rather than establishing a causal effect of sex, this report suggests that sex may modify disease expression in adult-onset CLN6 and that prominent psychiatric manifestations may signal a more aggressive clinical trajectory.

Amyloid-related imaging abnormalities (ARIA) with edema (ARIA-E) and with hemorrhage (ARIA-H) are common adverse effects of amyloid-targeting therapies (ATT), characterized on MRI by T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities and susceptibility-sensitive hypointensities, respectively. ARIA resulting from ATT is not commonly associated with reduced diffusion or acute infarcts. In this case series, we describe three patients with mild cognitive impairment due to Alzheimer's disease (AD) - a 75-year-old woman, a 74-year-old woman, and an 80-year-old man (APOE ε3/ε3, ε4/ε4, and ε3/ε4, respectively) - who developed ARIA accompanied by transient foci of reduced diffusion within the first six months of donanemab treatment, without permanent T2/FLAIR correlates. The diffusion-restricting lesions may represent ischemic infarcts, although the lack of permanent T2/FLAIR correlate is atypical. Clinicians should be aware that reduced diffusion may accompany ARIA. The course can be highly dynamic, and both the clinical presentation and management implications may vary.

Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder characterized by progressive dementia and multiple bone cysts. The known pathogenic genes include TYRO protein tyrosine kinase binding protein (TYROBP) on chromosome 19q13.1 and triggering receptor expressed on myeloid cells 2 (TREM2) on chromosome 6p21.1. Until now, no case related to TYROBP gene mutation has been reported in the Chinese population. We report a 39-year-old Chinese Han patient who presented with early-onset dementia and cystic bone lesions. Brain magnetic resonance imaging showed extensive cerebral atrophy with ventricular enlargement and diffuse, symmetric white matter lesions. Whole-exome sequencing identified a nonsense mutation, c.214C > T (p.Arg72Ter), in the TYROBP gene. Minigene experiments suggested that this variant may partially affect TYROBP splicing, providing supplementary transcript-level evidence for NHD. This is the first genetically confirmed case of NHD associated with a homozygous TYROBP c.214C > T (p.Arg72Ter) variant in the Chinese population. Our findings expand the mutation spectrum of NHD and provide new reference evidence for its molecular diagnosis and genetic counseling.

Language lateralization (LL) is a key aspect for preoperative surgical planning in patients with brain tumors. Crossed cerebro-cerebellar (CCC) activation, derived from functional magnetic resonance imaging (fMRI), guides LL determination. Structural features, such as gray matter volume (GMV), may provide complementary information on structural asymmetries associated with LL. However, the literature suggests that LL may change after surgery, and less is known about its variation over repeated surgeries. This case study aims to characterize LL in a patient with a recurrent glioma using both functional and structural measures. The case is a 33-year-old woman who underwent three intraoperative awake speech mapping tumor resections. Conventional MRI and fMRI were acquired before each surgery: 2017 (T1), 2020 (T2), and 2023 (T3). CCC activation was used as a functional marker of LL, and GMV was used to examine structural asymmetries. Linguistic and cognitive functions were examined pre-and postoperatively. Although supratentorial activation patterns showed some variability, CCC activation consistently indicated left-hemisphere LL. Structural analyses revealed differential volumetric patterns between the ipsilateral and contralateral language regions. Combining functional and structural measures, such as CCC activation and GMV analysis, may provide complementary information for assessing LL in patients undergoing repeated surgeries.

Partial locked-in syndrome (PLIS) is a rare stroke presentation in which preserved consciousness is masked by severe motor impairment, potentially leading to misinterpretation as encephalopathy. We report a patient in her early seventies with vascular risk factors and a prior pontine infarct who presented with acute quadriplegia and mutism. Initial clinical impressions raised concern for altered mental status. However, subsequent neurological examination demonstrated preserved awareness, with consistent eye tracking and command following through head movements. Examination showed bifacial and bulbar weakness, severe dysarthria, and minimal right arm movement. MRI demonstrated new infarcts in the left cerebral peduncle, posterior limb of the internal capsule, thalamus, and temporal lobe, superimposed on a prior pontine lesion. This distributed but strategically located pattern of injury affected bilateral corticospinal pathways and explained the profound motor impairment despite preserved consciousness. This case highlights how PLIS may mimic encephalopathy in the acute care setting and underscores the importance of structured bedside assessment for detecting preserved awareness in mute or immobile patients. Early recognition has implications for airway management, stroke evaluation, communication strategies, and prognostic counseling.