Satoki Hanayama

BACKGROUND: Acute intermittent porphyria (AIP) is a rare but treatable disease. COVID-19 has various possible complications including posterior reversible encephalopathy syndrome (PRES). COVID-19 was reported to trigger an acute attack in patients with acute hepatic porphyria (AHP). The pathophysiology of AHP-associated PRES is not fully elucidated. CASE PRESENTATION: A 31-year-old Vietnamese female initially presented with seizures, severe hyponatremia, and hypertension after COVID-19. Despite the initial treatment, she had recurrent seizures and developed PRES as confirmed by magnetic resonance imaging. Further investigations revealed a genetic mutation of c.517 C > T in HMBS, leading to a diagnosis of AHP. Treatment with hemin significantly improved her symptoms and corrected her electrolyte imbalance. CONCLUSIONS: This case highlights the potential for COVID-19 to trigger acute attacks in patients with underlying porphyria, potentially leading to complications such as PRES. Also, we observed elevated catecholamine levels during an acute porphyria attack and PRES, suggesting their involvement in the pathogenesis of AIP-associated PRES. Clinicians should consider the possibility of porphyria in patients with COVID-19-associated PRES, especially when they present with gastrointestinal and neuropsychiatric symptoms.

Background Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) and tau protein accumulation, reflected in cerebrospinal fluid (CSF) analysis. However, the interplay among CSF biomarkers, neuroimaging, and cognition remains elusive. Objective To explore associations among neuroimaging features, CSF biomarkers, and cognitive performance in AD. Methods Sixty patients with clinically diagnosed AD showing Aβ pathology in CSF underwent neuroimaging assessment of gray matter volume using T1-weighted MRI, cerebral blood flow (CBF) using single-photon emission computed tomography, and white matter hyperintensities (WMHs) using T2-weighted or fluid-attenuated inversion recovery images. Partial least square (PLS) regression identified imaging findings related to CSF biomarkers and Mini-Mental State Examination (MMSE) scores. Structural equation modeling (SEM) explored associations between factors with variable importance in projection (VIP) scores above 1.5 in PLS regression. Results Lateral temporal and occipital gray matter volumes positively correlated with MMSE scores (VIP = 1.95, 1.53), whereas WMHs in parietal and frontal periventricular regions were negatively associated with CSF Aβ 42 (VIP = 1.54, 1.58). Lateral temporal CBF was also associated with MMSE scores (VIP = 2.22). SEM analysis showed that reduced CSF Aβ 42 was linked to increased WMHs (p = 0.028), which correlated with each region (p < 0.005) and explained the reduced MMSE score (p = 0.013). Lateral temporal CBF correlated with temporo-occipital gray matter volume (p < 0.001) and influenced the MMSE score (p < 0.001). Conclusions This study suggests that amyloid pathology via WMHs and neurodegeneration of the lateral temporal lobe independently contribute to cognitive impairment in patients with AD.

Background: Neurological sequelae of coronavirus disease 2019 (COVID-19) include inflammatory myelopathies. Among these, magnetic resonance imaging (MRI)-negative myelitis- defined as normal spinal cord MRI findings despite compatible clinical features-presents diagnostic and therapeutic challenges. Case presentation: A 22-year-old Japanese woman developed progressive distal paresthesia, gait disturbance, bladder and rectal dysfunction, and sensory loss approximately three months after COVID-19. Neurological examination presented with pyramidal tract signs and sensory deficits in both lower limbs. Cerebrospinal fluid oligoclonal bands were positive. Brain MRI showed subtle corticospinal tract hyperintensities, whereas spinal MRI findings remained normal throughout the course. Somatosensory-evoked potentials (SEP) demonstrated absent right N20 and bilateral P37 responses, localizing dysfunction to the thoracic cord. Treatment with intravenous methylprednisolone pulse therapy with plasma exchange resulted in marked clinical recovery and SEP normalization, with only mild residual paresthesia at two-year follow-up. Discussion: The present case illustrates the clinical utility of SEPs for monitoring disease activity and establishing objective criteria for treatment escalation in post-COVID-19 MRI-negative myelitis. Although MRI-negative myelitis can be observed in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), lupus myelitis, and glial fibrillary acidic protein (GFAP) astrocytopathy, post-COVID-19 myelitis lacks specific biomarkers, complicating both diagnosis and treatment. A review of 20 reported cases of post-COVID-19 MRI-negative myelitis revealed a mean age of 54.4 years, a male-to-female ratio of 3:2, frequent bladder and rectal disturbances and paresis (85% each), high severity (63.2%), a median infection-to-neurological interval of 28 days, oligoclonal bands in 25% (4/16), multiple immunotherapies in 66.7%, and marked improvement or recovery in 66.7%. Conclusion: In post-COVID-19 MRI-negative myelitis, SEPs offer critical diagnostic and prognostic information. Early recognition and timely escalation of combination immunotherapy may optimize neurological outcomes.