Clinical Neuropathology最新文献

Aims: This work aims at supporting structured neuropathological assessment and early case identification for human bornavirus encephalitis. It summarizes current neuropathological and immunopathogenic findings of infection with Borna disease virus 1 (BoDV-1) in humans, complemented by comparative data from animal dead-end hosts.

Materials and methods: This narrative review is based on a targeted literature search in PubMed and Google Scholar. Of 114 identified records (PubMed: 62; Google Scholar: 52), 40 remained after duplicate removal. Following abstract and full-text screening, 16 studies, published between 1999 and 2025, were included.

Results: BoDV-1 encephalitis displays a largely uniform histopathological pattern, typically presenting as lymphocytic, sclerosing panencephalomyelitis with astroglial and microglial activation, and detection of intranuclear inclusions. In animals olfactory and limbic structures are predominantly affected, whereas in humans, the disease frequently extends to additional regions, particularly the basal ganglia.

Conclusion: In both human and animal dead-end hosts, BoDV-1 encephalitis shows a consistent histomorphological profile that allows reliable recognition based on characteristic neuropathological features and distribution. Definitive diagnosis requires specific detection of BoDV-1, most commonly facilitated by immunohistochemistry.

Background: West Nile virus (WNV) is now endemic in Europe and continues to spread to several countries, with strains 1 and 2 primarily responsible for outbreaks. According to the European Centre for Disease Prevention and Control (ECDC), Italy accounts for the majority of locally acquired cases and West Nile neuroinvasive disease (WNND).

Case report: We present the first case described in Italy and Europe of WNND-related Guillain-Barré syndrome (GBS). Phylogenetic analysis showed that the genome belonged to the WNV-2, sublineage 2a, clustering within sequences from genomes originating mainly from Hungarian 578/10 strain, a particularly virulent strain.

Conclusion: The first case of GBS as a presentation of WNND in a European patient is reported, along with a review of all previously published cases of GBS related to WNND. The United States Centers for Diseases Control and Prevention (CDC) documented 13% of WNV infections manifest as GBS, with a gradual and slow improvement, often with residual neurologic deficits of varying severity. Physicians should be aware that the presentation of a patient to an emergency department with GBS, during a certain epidemiological period of the year, should raise the clinical suspicion that the GBS may be related to a WNND.

Background: Multiple system atrophy (MSA) is a progressive adult-onset synucleinopathy that remains difficult to diagnose clinically, particularly in younger patients and during early disease stages. Brainstem nuclei degeneration resulting in reduced monoamines in cerebrospinal fluid (CSF) analysis may further complicate diagnostic interpretation.

Objectives: To describe a clinicopathologic case of early-onset MSA found to have decreased CSF monoamines suggestive of a primary neurotransmitter synthesis disorder.

Materials and methods: Clinical records, neuroimaging findings, CSF neurotransmitter analysis, and postmortem neuropathologic examination were reviewed.

Results: A 41-year-old woman developed rapidly progressive parkinsonism, dystonia, dysphagia, and speech impairment. Broad CSF analysis was significant for reduced homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and tetrahydrobiopterin, raising concern for a monoamine synthesis defect and prompting treatment for sepiapterin reductase deficiency (SRD). Despite directed therapy, neurologic decline continued. Postmortem examination demonstrated neuropathologic findings consistent with MSA, parkinsonian subtype (MSA-P). Early cortical and allocortical amyloid-β deposition corresponding to Thal phase 2 was also identified. No additional proteinopathies were present.

Conclusion: Degeneration of dopaminergic and serotonergic nuclei in MSA can reduce CSF monoamine metabolite levels and mimic disorders of neurotransmitter biosynthesis despite correlation with tetrahydrobiopterin levels. This case highlights a potential diagnostic pitfall when interpreting CSF neurotransmitter studies in adults with parkinsonism.

Objective: The medial accessory olivary nucleus (MAO), a distinct but inconsistently present subnucleus of the human inferior olivary complex, is poorly characterized despite its proposed role in cerebellar motor circuitry. We aimed to investigate its structural asymmetry, functional correlates, and pathological vulnerability in humans.

Materials and methods: We performed high-resolution histological analysis (Nissl and immunohistochemistry) in 35 neurologically normal brains to quantify MAO volume and neuronal numerical density and relate these to handedness and lifetime manual dexterity. In a separate cohort of 20 Parkinson's disease (PD) brains (Braak stages 4 - 6), we compared MAO neuronal numerical density and α-synuclein pathology to age-matched controls.

Results: The MAO was identifiable in 74% (26/35) of neurologically normal cases. A significant volumetric asymmetry was present (p < 0.01), with larger MAO volume contralateral to the dominant hand, and the asymmetry index correlated with lifetime manual dexterity scores (r = 0.54, p = 0.002). PD brains showed a 43% reduction in MAO neuronal numerical density versus controls (p < 0.001) and more severe α-synuclein pathology (median grade 3 vs. 0, p < 0.001).

Conclusion: The MAO may be a neuroanatomically variable but functionally lateralized structure that appears linked to fine motor control and may exhibit selective vulnerability in PD.

Background: Episodic ataxias (EAs) are rare autosomal-dominant channelopathies presenting with recurrent attacks of ataxia and variable neurological features. While MRI studies suggest mild cerebellar atrophy in some patients, detailed neuropathological descriptions are lacking.

Materials and methods: We examined postmortem brains and spinal cords from two genetically confirmed patients: EA1 (KCNA1 Val174Phe mutation) and EA2 (CACNA1A A253Y mutation). Routine histology and immunohistochemistry were performed.

Results: In EA1, the cerebellar vermis and hemispheres showed narrowing of the folia, segmental Purkinje cell loss, Bergmann gliosis, and scattered torpedoes. The dentate nucleus contained focal lipofuscin-laden macrophages and Rosenthal fibers. Concurrently, α-synuclein pathology (Braak stage 3) was also present, along with sparse age-related tau tangles and minimal vascular amyloid. In EA2, only focal Purkinje cell loss was detected, but novel p62-positive axonal and dendritic inclusions were observed in the cerebellar cortex and inferior olive. No additional α-synuclein, tau, or amyloid pathology was found. A concurrent glioblastoma was identified as the immediate cause of death.

Conclusion: These are the first detailed autopsy reports of EA1 and EA2. Both revealed cerebellar pathology, with EA1 showing more pronounced Purkinje cell degeneration, while EA2 demonstrated previously undescribed p62-positive inclusions. These findings expand the clinicopathological spectrum of EAs and highlight the value of postmortem studies in elucidating underlying disease mechanisms.

Noncoding GGC repeat expansion of various genes leads to oculopharyngodistal myopathy (OPDM), an adult-onset progressive neuromuscular disorder characterized by ophthalmoplegia, pharyngeal dysfunction, and distal limb muscular weakness. Recently, clinical overlap among noncoding GGC repeat-associated neuromuscular diseases, including OPDM, fragile X-associated tremor/ataxia syndrome (FXTAS), and neuronal intranuclear inclusion disease (NIID), has been recognized. Here, we present an autopsy case of OPDM with GIPC1 mutation (OPDM2) in a 56-year-old man. Histopathological studies revealed loss of myelinated fibers in the cerebrum and the presence of neuronal and glial intranuclear inclusions, which are commonly observed in FXTAS and NIID. Numerous intranuclear inclusions in oligodendrocytes were a characteristic feature of our autopsied case. Although GGC repeat expansions in distinct genes produce similar neuropathological findings, such as neuronal and glial intranuclear inclusions, the affected cell populations differ.

This review describes the clinically and genetically heterogenous group of 52 Spinocerebellar ataxias (SCAs). After a brief description of the epidemiology and clinical spectrum, this review highlights the functional neuroanatomy, the need for sufficient sampling based on this knowledge, and showcases examples of neuropathology. In addition, a comprehensive overview of the pathogenesis of the different forms of spinocerebellar ataxias (SCAs) is given.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating central nervous system disease caused by John Cunningham virus (JCV) reactivation in immunosuppressed patients. Although classically associated with advanced HIV infection, PML also occurs in patients with hematological malignancies, organ transplants, or on immunomodulatory therapies. The mortality rate can be high, ranging from 20 to 90%, depending on the underlying condition. Clinical presentation is variable, depending on the site of brain involvement, and diagnosis requires integration of clinical, radiological, pathological, and virological findings [1, 2, 3, 4]. We present the case of a 69-year-old HIV-negative woman with progressive neurological decline, whose initial workup focused on a suspected lymphoproliferative disorder. This case demonstrates the classical neuroimaging and neuropathological features of PML.

Intraoperative diagnostics in neuro-oncology face a critical gap between the morphological limitations of hematoxylin-eosin staining or toluidine blue staining and the time-intensive nature of conventional immunohistochemistry (IHC). This delay hinders real-time surgical decision-making, particularly in distinguishing gliomas, metastases, and lymphomas. To address this, we validated a novel, rapid IHC protocol utilizing directly conjugated polymerized horseradish peroxidase (pHRP) antibodies, designed to deliver results in under 30 minutes. We evaluated the performance of pan-cytokeratin (pan-CK), glial fibrillary acidic protein (GFAP), and cluster of differentiation 20 (CD20) antibodies on 115 intraoperative frozen tissue samples. Staining quality was assessed using a 4-tiered scoring system (from 0 to 3+). The cytoplasmic markers GFAP and pan-CK demonstrated excellent robustness and reliability, achieving mean scores of 2.6 and 2.47, respectively, with over 68% of cases showing strong, specific staining (3+). The membrane-bound marker CD20 showed more variability (mean score 2.07), highlighting the influence of antigen localization on this rapid protocol. Our findings demonstrate that this rapid IHC method is a viable and highly effective tool for the intraoperative differentiation of central nervous system tumors, particularly for cytoplasmic antigens. By providing crucial morphological information in near real-time, this approach has the potential to significantly enhance diagnostic precision during surgery, enabling immediate, tailored therapeutic strategies and improving patient outcomes.