Annals of Clinical and Translational Neurology最新文献

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is caused by biallelic pathogenic variants in the SACS gene. We report the clinical, radiologic and neurophysiologic features of a pair of half-siblings who presented with progressive cerebellar ataxia, peripheral neuropathy and upper motor neuron signs. After significant diagnostic delay, genetic testing revealed both harboured a shared, paternally inherited microdeletion encompassing the SACS gene, and each harboured a different single nucleotide variant in SACS, each likely maternally inherited. Recognition of the clinical and radiologic phenotype of ARSACS may facilitate early diagnosis of this disorder even in the face of uncommon inheritance patterns.

In this study, we analyzed biomarkers of neuronal, glial, and vascular injury in longitudinal paired samples of blood and cerebrospinal fluid after prophylactic cranial irradiation in patients with small cell lung cancer. Neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAP) increased in serum and cerebrospinal fluid after irradiation; serum NfL correlated with cerebrospinal fluid values, apparently independent of blood-brain barrier function, whereas GFAP correlations were weaker. Although several patients developed brain metastases, linear mixed model results were consistent with an independent effect of radiotherapy on serum NfL and GFAP. Serum placental growth factor also rose and correlated with the albumin ratio. Our results support a radiotherapy-associated increase of NfL and GFAP in blood.

This case details a 35-year-old man with no past medical history who presents with acute paraparesis and urinary retention in the setting of progressive paresthesias and weakness of his lower and upper extremities over several months. He was found to have longitudinally extensive transverse myelitis involving the cervical to mid-thoracic cord with concomitant findings of mediastinal and hilar lymphadenopathy. An extensive serum and cerebrospinal fluid (CSF) workup of possible autoimmune, paraneoplastic, infectious, and toxic/metabolic etiologies was overall nonrevealing, but an endobronchial ultrasound-guided biopsy of the enlarged hilar lymph nodes revealed noncaseating granulomas. The patient demonstrated significant improvement after completing two courses of pulse-dose steroids and was ultimately discharged to intensive inpatient rehabilitation for further treatment.

Objective: Disrupted neurofluid regulation may contribute to neurodegeneration in Huntington disease (HD). Because neurofluid pathways influence waste clearance, inflammation, and the distribution of central nervous system (CNS)-delivered therapeutics, understanding their dysfunction is increasingly important as targeted treatments emerge. We aimed to evaluate structural and physiological changes in two key neurofluid components, the choroid plexus (ChP), which produces cerebrospinal fluid (CSF), and the parasagittal dural (PSD) space, a major CSF outflow pathway, across the HD spectrum and in relation to CSF flow dynamics.

Methods: PSD and ChP volumes were assessed using a validated deep learning pipeline on 3-Tesla T₂-weighted and FLAIR MRI. CSF flow at the cerebral aqueduct was measured with phase contrast MRI, and ChP perfusion was quantified using pseudo-continuous arterial spin labeling MRI. Linear regression models assessed the relationships between PSD and ChP volume, CSF flow kinetics, ChP hemodynamics, disease severity, disease exposure, and disease presentation, adjusting for age, sex, and intracranial volume.

Results: 80 HD participants and 65 age-matched healthy controls were included. HD showed significantly larger ChP and PSD volumes (p < 0.01) and reduced ChP perfusion (p < 0.01). Greater CAG repeat expansion correlated with larger PSD and ChP volume and lower ChP perfusion (p < 0.01). These alterations were associated with worse motor impairment (p < 0.01).

Interpretation: HD is associated with structural and functional alterations in neurofluid pathways. These findings suggest relevance for disease mechanisms and for optimizing CSF-based therapeutic delivery, highlighting the need for further mechanistic studies.

A 73-year-old man presented with progressive weakness and atrophy predominantly affecting the distal finger flexors and quadriceps muscles. Electrophysiological studies demonstrated mixed myogenic and neurogenic features. Muscle MRI showed inflammatory changes, and muscle biopsy revealed granulomatous myositis with histologic features characteristic of inclusion body myositis (IBM), including rimmed vacuoles, TDP-43 mislocalization, and autophagy activation. Additional extensive laboratory and imaging workup ruled out systemic etiologies. An empiric trial of high-dose corticosteroids yielded no clinical improvement. The diagnostic challenge stemmed from the broad differential diagnosis of granulomatous myositis and the possibility that non-IBM etiologies might be responsive to immunosuppressive treatment. This case underscores the importance of integrating clinical, electrophysiologic, radiologic, and histopathologic findings to accurately diagnose and manage granulomatous myositis.

Introduction: Spinal cord infarction (SCI) is a rare but devastating myelopathy, characterized by a high disability rate and an unfavorable prognosis. It has often been underdiagnosed and misdiagnosed as idiopathic transverse myelitis (ITM). This study aimed to describe the clinical features, radiological biomarkers, treatments, and functional outcome of SCI, distinguishing it from ITM.

Methods: A retrospective observational cohort study included patients who met the diagnostic criteria of SCI and ITM from January 2019 to October 2024. The clinical, radiological data, and diagnosis were recorded, and the functional outcomes were reached via telephone and face-to-face evaluations. Univariate analysis was used to differentiate the two groups.

Results: During the study period, a total of 22 SCI patients with a median age of 53.0 years (interquartile range (IQR): 41.8 to 60.2) were enrolled. Thirteen patients underwent the diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) sequence, among whom 12 were confirmed as having definite SCI. Compared with ITM, SCI has the following characteristics. The time from onset to nadir in SCI is much shorter, mostly within 6 h (p < 0.001). On sagittal MRI, SCI often manifests as linear lesions, while ITM tends to present as patchy and fusiform lesions (p < 0.001). We have also defined a lesion characteristic of SCI based on T2-weighted sequences, termed the "eccentric sign". Moreover, patients with SCI generally have a poorer prognosis and higher dependence.

Conclusions: SCI can be diagnosed and differentiated from ITM based on clinical features and radiological signs.

Background: SOX1 antibody-positive paraneoplastic neurological syndromes (PNS) exhibit significant population-specific clinical heterogeneity. While Western cohorts predominantly manifest Lambert-Eaton myasthenic syndrome (65%-80%), comprehensive clinical characterization and treatment response data in Asian populations remain critically limited.

Methods: We conducted a single-center retrospective case series analyzing 13 consecutive patients with SOX1 antibody-positive PNS treated at Guangdong Sanjiu Brain Hospital from January 2019 to December 2024. SOX1 antibodies were confirmed using commercial immunoblot assay. Primary endpoints included treatment response (≥ 1-point improvement on modified Rankin Scale [mRS]) and functional recovery (mRS ≤ 2). Statistical analyses employed Fisher's exact tests and Mann-Whitney U tests.

Results: Among 13 patients (median age 61 years [IQR 56-67], 53.8% female), neuropsychiatric presentations predominated, including seizures (46.2%) and psychiatric symptoms (30.8%), with combined neuropsychiatric manifestations occurring in 53.8% of patients. Co-existing neuronal antibodies were identified in 15.4% of cases (GABAB receptor, LGI1). Malignancy was confirmed in 30.8% of patients. Immunotherapy recipients (n = 7) demonstrated significantly superior functional outcomes compared to non-treated patients: median 3-month mRS 0 (IQR 0-0) versus 3 (IQR 3-3), p = 0.03. Treatment response rates were 85.7% versus 33.3% (p = 0.103).

Conclusions: Chinese patients with SOX1 antibody-positive PNS demonstrate a neuropsychiatric-predominant phenotype (53.8%), contrasting markedly with Western cohorts. Early immunotherapy administration was associated with superior functional outcomes (median 3-month mRS: 0 vs. 3, p = 0.03). These findings support comprehensive neuronal antibody profiling and early immunotherapy consideration in patients presenting with neuropsychiatric manifestations.

Objective: Spinocerebellar ataxia type 3 (SCA3) is a genetically defined ataxia. The Scale for Assessment and Rating of Ataxia (SARA) is a clinician-reported outcome that measures ataxia severity at a single time point. In its standard application, SARA fails to capture short-term fluctuations, limiting its sensitivity in trials. To overcome this, we employed SARA^home, a video-based, self-administered tool for high-frequency, remote ataxia assessment.

Methods: We assessed feasibility and validity of SARA^home in 65 SCA3 patients from seven centers. Participants recorded SARA^home twice daily for 14 days using a mobile e-health app. We analyzed adherence, intraindividual fluctuations and their predictors, and evaluated sensitivity to change in a longitudinal substudy of 11 patients.

Results: Adherence to the study protocol was generally high (80.2%) with valid scores in 79.2% of 1459 recordings. Maximum adherence occurred over a 4-day period (84.8%). Fluctuations ranged 3.0 points between lowest and highest scores (IQR: 2.5-4.5) and 1.0 point based on score IQRs (IQR: 0.5-1.5), corresponding to 10.7% and 3.6% of the maximal SARA^home score. Fluctuations showed rough agreement with patient global impression. Greater disease severity and longer CAG repeats were associated with smaller relative fluctuations. Over a median follow-up of 411 days, SARA^home showed higher sensitivity to change than conventional SARA (SRM: 0.67 vs. 0.37).

Interpretation: SARA^home is a feasible, innovative video-based tool for remote, high-frequency monitoring of ataxia severity. A 4-day recording effectively captures relevant fluctuations and enhances sensitivity to change, supporting its use in future SCA3 trials.

The timing for initiating immunotherapy in patients with glutamic acid decarboxylase 65 (GAD65) antibody-associated epilepsy is a challenge. We used the translocator protein radioligand [¹⁸F]DPA-714 and PET to evaluate brain microglial activation. [¹⁸F]DPA-714 PET brain images of 11 patients with GAD65 antibody-associated epilepsy and seven controls were analyzed. Patients with acute symptomatic seizures presented higher [¹⁸F]DPA-714 SUVR in the hippocampus than did controls and patients with chronic temporal lobe epilepsy. Our findings highlight that [¹⁸F]DPA-714 PET/MRI represents a useful tool to assess neuroinflammation in patients with GAD65 antibody-associated epilepsy.

Adrenoleukodystrophy is a rare inherited peroxisomal disease caused by pathogenic variants in the ABCD1 gene located on the X chromosome. Although the most severe central nervous system and adrenal complications typically affect only men with adrenoleukodystrophy, the majority of women develop myeloneuropathy symptoms in adulthood. In observational studies of women with adrenoleukodystrophy, several clinical rating scales have been used to assess disease manifestations and capture differences between asymptomatic and symptomatic women. To facilitate development of treatments to address symptoms in women, there is a need to identify clinical outcome measures that can sensitively assess disease progression and treatment responses. The goals of this scoping review were to: (1) identify and review clinically relevant assessment scales that have been utilized to capture disease manifestations in women with adrenoleukodystrophy, and (2) provide recommendations on key objectives for further research.