Journal of Clinical Neurology最新文献

Background and purpose: The coast of Kyushu Island on Ariake Sea in Japan is known to be an accumulation area for patients with a proline-to-leucine substitution mutation at residue 102 (P102L) of the human prion protein gene (PRNP), which is associated with Gerstmann-Sträussler-Scheinker disease. We designated this geographical distribution as the "Ariake PRNP P102L variant." The purpose of this study was to characterize the clinical features of this variant.

Methods: We enrolled patients with the PRNP P102L variant who were followed up at the Saga University Hospital from April 2002 to November 2019. The clinical information of patients were obtained from medical records, including clinical histories, brain magnetic resonance imaging (MRI), and electroencephalography (EEG). A brain autopsy was performed on one of the participants.

Results: We enrolled 24 patients from 19 family lines, including 12 males. The mean age at symptom onset was 60.6 years (range, 41-77 years). The incidence rate of the Ariake PRNP P102L variant was 3.32/1,000,000 people per year in Saga city. The initial symptoms were ataxia (ataxic gait or dysarthria) in 19 patients (79.2%), cognitive impairment in 3 (12.5%), and leg paresthesia in 2 (8.3%). The median survival time from symptom onset among the 18 fatal cases was 63 months (range, 23-105 months). Brain MRI revealed no localized cerebellar atrophy, but sparse diffusion-weighted imaging abnormalities were detected in 16.7% of the patients. No periodic sharp-wave complexes were identified in EEG. Neuropathological investigations revealed uni- and multicentric prion protein (PrP) plaques in the cerebral cortex, putamen, thalamus, and cerebellum of one patient. Western blot analysis revealed 8-kDa proteinase-K-resistant PrP.

Conclusions: This is the first report of the accumulation area of a PRNP P102L variant on the coast of Ariake Sea. The Ariake PRNP P102L variant can be characterized by a relatively long disease duration with sparse abnormalities in brain MRI and EEG relative to previous reports. Detailed interviews to obtain information on the birthplace and the family history of related symptoms are important to diagnosing a PRNP P102L variant.

Background and purpose: Early- and late-onset Alzheimer's disease (EOAD and LOAD, respectively) share the same neuropathological hallmarks of amyloid and neurofibrillary tangles but have distinct cognitive features. We compared structural brain connectivity between the EOAD and LOAD groups using structural network efficiency and evaluated the association of structural network efficiency with the cognitive profile and pathological markers of Alzheimer's disease (AD).

Methods: The structural brain connectivity networks of 80 AD patients (47 with EOAD and 33 with LOAD) and 57 healthy controls were reconstructed using diffusion-tensor imaging. Graph-theoretic indices were calculated and intergroup differences were evaluated. Correlations between network parameters and neuropsychological test results were analyzed. The correlations of the amyloid and tau burdens with network parameters were evaluated for the patients and controls.

Results: Compared with the age-matched control group, the EOAD patients had increased global path length and decreased global efficiency, averaged local efficiency, and averaged clustering coefficient. In contrast, no significant differences were found in the LOAD patients. Locally, the EOAD patients showed decreases in local efficiency and the clustering coefficient over a wide area compared with the control group, whereas LOAD patients showed such decreases only within a limited area. Changes in network parameters were significantly correlated with multiple cognitive domains in EOAD patients, but only with Clinical Dementia Rating Sum-of-Boxes scores in LOAD patients. Finally, the tau burden was correlated with changes in network parameters in AD signature areas in both patient groups, while there was no correlation with the amyloid burden.

Conclusions: The impairment of structural network efficiency and its effects on cognition may differ between EOAD and LOAD.

Single-pulse magnetic stimulation is the simplest type of transcranial magnetic stimulation (TMS). Muscle action potentials induced by applying TMS over the primary motor cortex are recorded with surface electromyography electrodes, and they are called motor-evoked potentials (MEPs). The amplitude and latency of MEPs are used for various analyses in clinical practice and research. The most commonly used parameter is the central motor conduction time (CMCT), which is measured using motor cortical and spinal nerve stimulation. In addition, stimulation at the foramen magnum or the conus medullaris can be combined with conventional CMCT measurements to evaluate various conduction parameters in the corticospinal tract more precisely, including the cortical-brainstem conduction time, brainstem-root conduction time, cortical-conus motor conduction time, and cauda equina conduction time. The cortical silent period is also a useful parameter for evaluating cortical excitability. Single-pulse magnetic stimulation is further used to analyze not only the central nervous system but also the peripheral nervous system, such as for detecting lesions in the proximal parts of peripheral nerves. In this review article we introduce four types of single-pulse magnetic stimulation-of the motor cortex, spinal nerve, foramen magnum, and conus medullaris-that are useful for the diagnosis, elucidation of pathophysiology, and evaluation of clinical conditions and therapeutic effects. Single-pulse magnetic stimulation is a clinically useful technique that all neurologists should learn.

Background and purpose: Monoclonal antibodies (mAbs) targeting calcitonin-gene-related peptide (CGRP) or its receptor (anti-CGRP-R) have been widely administered to patients with migraine who show inadequate responses to preventive medications. Among patients in whom a particular anti-CGRP-R mAb is ineffective, switching between different anti-CGRP-R mAbs can be the next option. Few studies have investigated treatment outcomes for antibody switching, especially between mAbs with the same target of the CGRP ligand. We aimed to determine the treatment outcome after switching between two anti-CGRP mAbs (galcanezumab to fremanezumab).

Methods: We identified migraine patients in a prospective headache clinic registry who received galcanezumab for ≥3 months and were switched to fremanezumab for a further ≥3 months at a single university hospital. We defined a treatment response as a ≥50% reduction in the number of days with a moderate or severe headache at the third month of treatment relative to baseline. The treatment response after switching to fremanezumab was compared with the initial treatment response to galcanezumab.

Results: Among 21 patients identified in the registry, 7 (33.3%) were initial responders to galcanezumab. After switching to fremanezumab, 7 (33.3%) showed a treatment response. The treatment response rate was 28.6% in the initial responders and 71.4% in the nonresponders to galcanezumab (p>0.999).

Conclusions: Switching between anti-CGRP mAbs (galcanezumab to fremanezumab) yielded a treatment outcome comparable to that reported previously when switching from an anti-CGRP-R mAb (erenumab) to an anti-CGRP mAb (galcanezumab or fremanezumab). The treatment response to fremanezumab seems to be independent of the prior treatment response to galcanezumab. Our findings suggest that switching to another anti-CGRP mAb can be considered when a particular anti-CGRP mAb is ineffective or intolerable.

Human reflexes are simple motor responses that are automatically elicited by various sensory inputs. These reflexes can provide valuable insights into the functioning of the nervous system, particularly the brainstem and spinal cord. Reflexes involving the brainstem, such as the blink reflex, laryngeal adductor reflex, trigeminal hypoglossal reflex, and masseter H reflex, offer immediate information about the cranial-nerve functionality and the overall state of the brainstem. Similarly, spinal reflexes such as the H reflex of the soleus muscle, posterior root muscle reflexes, and sacral reflexes provide crucial information about the functionality of the spinal cord and peripheral nerves. One of the critical benefits of reflex monitoring is that it can provide continuous feedback without disrupting the surgical process due to no movement being induced in the surgical field. These reflexes can be monitored in real time during surgical procedures to assess the integrity of the nervous system and detect potential neurological damage. It is particularly noteworthy that the reflexes provide motor and sensory information on the functional integrity of nerve fibers and nuclei. This article describes the current techniques used for monitoring various human reflexes and their clinical significance in surgery. We also address important methodological considerations and their impact on surgical safety and patient outcomes. Utilizing these methodologies has the potential to advance or even revolutionize the field of intraoperative continuous monitoring, ultimately leading to improved surgical outcomes and enhanced patient care.

The relationship between infections and stroke has not been fully characterized, probably delaying the development of specific treatments. This narrative review addresses mechanisms of stroke linked to infections, including hypercoagulability, endothelial dysfunction, vasculitis, and impaired thrombolysis. SARS-CoV-2, the virus that causes COVID-19, may promote the development of stroke, which may represent its most severe neurological complication. The development of specific therapies for infection-associated stroke remains a profound challenge. Perhaps the most important remaining issue is the distinction between infections that trigger a stroke versus infections that are truly incidental. This distinction likely requires the establishment of appropriate biomarkers, candidates of which are elevated levels of fibrin D-dimer and anticardiolipin/antiphospholipid antibodies. These candidate biomarkers might have potential use in identifying pathogenic infections preceding stroke, which is a precursor to establishing specific therapies for this syndrome.