Case report A 31-year-old previously healthy man who had sex with men presented with a two-day history of acute-onset dizziness, nausea, and vomiting. On admission, he was afebrile with generalized lymphadenopathy and a truncal and lower-limb rash. Neurological examination revealed no motor weakness or hyperreflexia, but he could not walk unassisted due to dizziness. Brain MRI diffusion-weighted imaging (DWI) showed characteristic V-shaped hyperintense lesions in the bilateral medial medulla (Fig. 1A) and at the pontomedullary junction (Fig. 1B). MR angiography (MRA) showed no stenosis or dissection of the basilar or vertebral arteries (VA) (Fig. 1C).

The distribution of amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) in the Kii Peninsula of Japan exhibits regional variations, with ALS/PDC in the Hohara focus closely resembling that in Guam and ALS in the Kozagawa focus. Recent structural analysis using cryo-electron microscopy revealed that the tau filaments in patients with ALS/PDC in Kii have a chronic traumatic encephalopathy (CTE) fold, confirming the disease's distinct pathological identity and commonality with the Guam focus. While the exact causal genes remain unidentified, research utilizing patient-derived induced pluripotent stem cells and proteomic analysis has uncovered endogenous mitochondrial dysfunction, specifically involving decreased expression of CHCHD2 and SSBP1. The presence of migrant cases further suggests that ALS/PDC is a multifactorial disorder triggered by environmental factors that influence genetic vulnerability. Although the incidence of ALS in Kozagawa and Hohara districtst has declined, new cases with PDC continue to emerge in Hohara. Identifying these modifiable environmental triggers is crucial for preventing and eradicating neurological disorders.

Difficulty walking is a common complaint in neurological practice which may arise from a wide range of disorders of the central nervous system, peripheral nerves, or musculoskeletal system. Because human gait requires the complex integration of multiple neural and biomechanical processes, careful clinical assessment is essential to achieve accurate diagnosis. In this review, we outlined a practical approach for patients presenting with walking difficulties. Emphasis is placed on the importance of detailed history-taking and neurological examination, including observation of gait, posture, gait initiation, and turning. We further summarize the key clinical features of the major organic causes of gait disturbance, such as lower limb weakness, pyramidal tract disorders, and Parkinsonian syndromes. Functional gait disorder is an important and increasingly recognized cause of gait disturbance. Recognizing the positive clinical signs and characteristic variability in symptoms is essential for appropriate diagnosis and management. Careful clinical evaluation remains the cornerstone for assessing gait disorders, and diagnostic tests should be used to confirm the clinical diagnosis based on the history and neurological examination.

When diagnosing dementia disorders, obtaining a detailed medical history and identifying relevant findings on physical and neurological examinations are fundamental. It is essential to assess cognitive function, neurological symptoms and signs, and dementia severity; conduct additional tests; and establish a differential diagnosis. With the widespread use of anti-amyloid antibody therapies, mild cognitive impairment (MCI) due to Alzheimer's disease (AD) and early-stage AD must not be overlooked. When evaluating patients with dementia who present with diverse symptoms, clinicians must consider neurological signs, findings from diagnostic tests, and the clinical course to establish an accurate diagnosis and guide appropriate treatment.

In the examination of patients with "lack of strength", abnormalities in motor units (α motor neurons, myelinated fibers, neuromuscular junctions, and muscle fibers), spinal cord-mediated neurons, projections that descend the spinal cord to control motor units (corticospinal tract, corticoreticular tract, and reticulospinal tract), and autonomic nerves, are considered, and physiological changes, diseases, and external factors are investigated. Appropriate assessment of muscle strength, investigations for pyramidal tract signs, appropriate expression of pathology, blood sampling, needle electromyography, and magnetic resonance imaging/magnetic resonance angiography of the head, are desirable.

Trembling/shaking is among the most common complaints encountered in general or neurological clinics. The differential diagnosis of this symptom is important as it can be caused by various conditions and neurological diseases. Essential tremor (ET) is a dominantly inherited disorder that manifests as a bilateral fine (>8Hz) postural tremor. Physiological tremor can develop in patients with sympathetically activated conditions, such as hyperthyroidism, fever, anxiety, and muscle fatigue, in addition to being induced by many drugs. Patients with Parkinson's disease may demonstrate lateralized, moderately fast (4-6Hz) resting and postural tremors. Rubral (midbrain) tremors in the arms with low frequency (3Hz) oscillation or palatal myoclonus may suggest lesions within the Guillain-Mollaret's triangle, which comprises the contralateral midbrain rubral nucleus, contralateral medullary inferior olivary nucleus, and ipsilateral cerebellar dentate nucleus. Intension (terminal) tremor is defined as an action tremor showing an amplitude increases towards the end of the movement to touch a target, as in the finger-nose-finger test. Orthostatic tremor (also termed shaky legs syndrome) is a variant of ET involving the legs observed only in the standing still position. In conclusion, a precise diagnosis of symptoms allows the management of the condition according to its causal mechanism.

This review provides a practical approach to evaluating and managing patients presenting with numbness and pain in the extremities. It emphasizes that careful history-taking and neurological examination remain the foundation of anatomic localization before imaging or electrophysiological studies are considered. The review summarizes the epidemiology, differential diagnosis, appropriate laboratory testing and neurophysiological investigations, indications for specialist referral, and current treatment strategies. Particular attention is given to distinguishing among nociceptive pain, neuropathic pain, and the recently recognized category of nociplastic pain because each requires a different therapeutic approach. The review also discusses chronic sensory symptoms frequently encountered in older adults, including patients with idiopathic distal sensory polyneuropathy and small-fiber neuropathy, in whom conventional investigations may be inconclusive. The review places these conditions within the spectrum of age-related peripheral nerve dysfunction while acknowledging emerging evidence for previously unrecognized etiologies. The review concludes that neurologists should focus not only on identifying serious neurological disorders but also on recognizing and validating patients' subjective sensory symptoms. A systematic clinical approach, combined with appropriate referral and individualized management, can substantially improve diagnostic accuracy and patient care in routine neurological practice.

Dizziness is one of the most common complaints encountered in outpatient clinical practice, and is associated with a wide range of underlying conditions, ranging from peripheral vestibular disorders to cerebrovascular disease, cardiovascular abnormalities, and psychological factors. Traditional classifications based on the quality of dizziness symptoms have inherent limitations in diagnostic accuracy. In contrast, the ATTEST approach, which structures clinical reasoning according to temporal profiles and triggering factors, has been shown to be useful. In this article, we outline the practical strategies for evaluating patients with dizziness and emphasize the importance of a thorough basic assessment and the avoidance of premature diagnostic closure to ensure an appropriate differential diagnosis.

Headache is one of the most common complaints encountered by neurologists. Therefore, it is important to rule out secondary headaches and correctly diagnose primary headaches, particularly migraines. The key features for the diagnosis of migraine are disturbances in daily life, aggravation due to physical movement, nausea, and light sensitivity. CGRP-related antibodies and CGRP-receptor antagonists have been introduced in Japan. These new medications have drastically improved migraine management outcomes. Appropriate diagnosis of migraine is essential to achieve optimal treatment. Cluster headache and related diseases are classified as trigeminal autonomic cephalalgias (TACs).

Microglia are resident immune cells of the central nervous system and play a central role in the pathogenesis of Alzheimer's disease (AD). Emerging evidence indicates that their functional state critically influences amyloid-β (Aβ) clearance, neuroinflammation, and disease progression. Tim-3, an immune checkpoint molecule, is highly expressed in microglia and functions as a key regulator of microglial homeostasis through the transforming growth factor-β (TGF-β)-Smad2 signaling pathway. Microglia-specific deletion of Tim-3 enhances phagocytic activity. Moreover, microglia-specific Tim-3 deficiency results in reduced Aβ deposition, decreased neurotoxicity, and improved cognitive performance in the 5xFAD mouse model of AD. These effects are not mediated by changes in Aβ production but rather by enhanced microglial clearance and remodeling of Aβ plaques into less toxic forms. Furthermore, single-cell analyses reveal that Tim-3 deficiency promotes a microglial state characterized by increased phagocytic capacity and reduced pro-inflammatory signaling. These findings suggest that Tim-3 acts as a functional checkpoint that limits beneficial microglial responses in AD and that targeting Tim-3 may therefore represent a promising therapeutic strategy for reprogramming microglia and improving disease outcomes.

Human visual cognition relies on two major streams that originate in the primary visual cortex: the ventral stream, which projects to the temporal lobe, and the dorsal stream, which projects to the parietal lobe. The ventral stream processes visual features such as shape, color, and texture, which are integrated to support object recognition. Within this stream, cortical regions are further organized by stimulus categories, including faces, places, words, and objects. The dorsal stream links vision with action and spatial behavior and can be subdivided into two functional substreams. The dorso-dorsal stream, centered on the superior parietal lobule, mediates online visuomotor control and reaching movements. The ventro-dorsal stream, associated with the inferior parietal lobule, contributes to object-related actions and spatial cognition. Damage to these streams produces dissociable clinical syndromes, such as visual agnosia following ventral stream damage and visual inattention after dorsal stream damage. While previous studies have mainly examined visual cognitive dysfunction due to focal lesions, neurodegenerative disorders also provide a unique opportunity to investigate visual network vulnerability. Conditions such as posterior cortical atrophy and dementia with Lewy bodies exhibit characteristic visuocognitive impairments that reflect systematic neuronal degeneration. Analyzing symptom profiles in such disorders may clarify the functional segregation of the visual streams.

Peripheral autonomic disorders, including autonomic neuropathies, lead to autonomic failure, a condition characterized by reduced autonomic function. The clinical manifestations involve multiple organ systems: in the cardiovascular system, orthostatic hypotension, postprandial hypotension, and supine/hypertension; in the gastrointestinal tract, gastroparesis, constipation, and diarrhea; and in the lower urinary tract, an underactive bladder. Peripheral autonomic disorders predominantly affect the postganglionic autonomic nerves, resulting in characteristic clinical features. The management of autonomic symptoms relies primarily on non-pharmacological interventions, with pharmacological therapy introduced when these measures are insufficient. This article reviews the clinical features, underlying pathophysiology, and treatment of symptoms associated with peripheral autonomic disorders.

Autoimmune autonomic ganglionopathy (AAG) is a peripheral neuropathy caused by immune-mediated synaptic transmission dysfunction in autonomic ganglia. Autoantibodies against the nicotinic ganglionic acetylcholine receptor (gAChR) have been detected in the sera of patients with AAG, and gAChR antibodies are considered pathogenic autoantibodies in AAG. In this review, we discuss recent clinical and research developments in AAG, focusing on the following: (1)reports on the clinical features of AAG and immunotherapy; (2)the association between COVID-19, COVID-19 vaccination, and autonomic dysfunction; (3)autonomic dysfunction as an immune-related adverse effect of immune checkpoint inhibitors in cancer treatment; and (4)new methods for measuring gAChR antibodies.

In addition to polyneuropathy, patients with hereditary transthyretin amyloidosis (ATTRv) often experience autonomic dysfunction, which reduces quality of life. Compared with patients with ATTRv from endemic areas, those from non-endemic areas rarely develop autonomic dysfunction as an initial symptom. Conversely, autonomic dysfunction can be a diagnostic red flag in patients from non-endemic areas without a family history. Autonomic dysfunction in patients with wild-type transthyretin amyloidosis (ATTRwt) has only recently been reported. However, further knowledge is needed to clarify its pathophysiology.

Diabetic autonomic neuropathy is a clinically important component of diabetic neuropathy involving the cardiovascular, gastrointestinal, genitourinary, sudomotor, pupillary, and glucose counterregulatory systems. Cardiovascular autonomic neuropathy (CAN) has been extensively studied and is clinically relevant because of its association with adverse cardiovascular and renal outcomes. Early CAN is frequently silent and may only be recognized by reduced heart rate variability or abnormal cardiovascular autonomic reflex testing. As CAN progresses, patients develop resting tachycardia, reduced exercise tolerance, orthostatic or postprandial hypotension, abnormal nocturnal blood pressure regulation, and perioperative hemodynamic instability. Non-cardiovascular manifestations include gastroparesis, bowel and bladder dysfunction, erectile dysfunction, sudomotor and pupillary abnormalities, and impaired hypoglycemic awareness. The underlying mechanisms involve chronic hyperglycemia, glycemic variability, dyslipidemia, insulin resistance, oxidative and mitochondrial stress, inflammation, microvascular injury, and impaired axon-glial support. Clinically, evaluation should begin with a systematic symptom review, neurological examination, supine and standing blood pressure measurements, and heart rate assessment, followed by organ-specific testing if indicated. Treatment was based on comprehensive risk factor control and symptom-directed management.