[Peripheral neuropathy associated with severe glial fibrillary acidic protein (GFAP) astrocytopathy: a case report].

A 44-year-old man was admitted due to a fever. He developed unconsciousness and respiratory failure, necessitating mechanical ventilation. After the administration of methylprednisolone and intravenous immunoglobulin for suspected autoimmune encephalitis, his consciousness and respiratory state improved. However, he exhibited pronounced tetraparalysis and impaired sensation below the neck. A spinal MRI revealed swelling of the entire spinal cord, indicating myelitis. Deep tendon reflexes were diminished in all extremities, and a nerve conduction study confirmed motor-dominant axonal polyneuropathy. Subsequently, he developed a fever and headache. Brain MRI demonstrated FLAIR hyperintensities in the basal ganglia and brain stem. CSF analysis for anti-glial fibrillary acidic protein (GFAP) antibody turned out positive, leading to the diagnosis of GFAP astrocytopathy. Although the steroid re-administration improved muscle strength in his upper limbs and reduced the range of diminished sensation, severe hemiparalysis remained. Severe GFAP astrocytopathy can be involved with polyneuropathy. Early detection and therapeutic intervention for this condition may lead to a better prognosis.

Deep-Learning-Based Analysis Reveals a Social Behavior Deficit in Mice Exposed Prenatally to Nicotine.

Cigarette smoking during pregnancy is known to be associated with the incidence of attention-deficit/hyperactive disorder (ADHD). Recent developments in deep learning algorithms enable us to assess the behavioral phenotypes of animal models without cognitive bias during manual analysis. In this study, we established prenatal nicotine exposure (PNE) mice and evaluated their behavioral phenotypes using DeepLabCut and SimBA. We optimized the training parameters of DeepLabCut for pose estimation and succeeded in labeling a single-mouse or two-mouse model with high fidelity during free-moving behavior. We applied the trained network to analyze the behavior of the mice and found that PNE mice exhibited impulsivity and a lessened working memory, which are characteristics of ADHD. PNE mice also showed elevated anxiety and deficits in social interaction, reminiscent of autism spectrum disorder (ASD). We further examined PNE mice by evaluating adult neurogenesis in the hippocampus, which is a pathological hallmark of ASD, and demonstrated that newborn neurons were decreased, specifically in the ventral part of the hippocampus, which is reported to be related to emotional and social behaviors. These results support the hypothesis that PNE is a risk factor for comorbidity with ADHD and ASD in mice.

CSF/plasma levels, transthyretin stabilisation and safety of multiple doses of tolcapone in subjects with hereditary ATTR amyloidosis.

PURPOSE: To investigate the effect of tolcapone on cerebrospinal fluid (CSF) transthyretin (TTR) tetramer stability in patients with hereditary transthyretin (ATTRv) amyloidosis. METHODS: A total of 9 patients were enrolled in the study (3 men, 50.3 ± 14.4 years old). Three patients had central nervous system (CNS) involvement. Patients were assigned to receive tolcapone 300 mg/day or 600 mg/day for 7 days. Plasma and CSF were collected at baseline and 2 h after the final tolcapone dose. RESULTS: The mean CSF tolcapone and 3-O-Methyltolcapone (3-OMT) concentration were 39.4 ± 36.3 ng/mL and 26.0 ± 4.9 ng/mL, respectively, after 7 days of tolcapone dosing. Tolcapone and 3-OMT were detected in the CSF of patients with or without CNS symptoms. The mean total study drug (tolcapone + 3-OMT) to TTR molar ratio in CSF was 1.15 ± 0.59. Orally administered tolcapone significantly increased CSF TTR concentration and decreased monomer content under semi-denaturing conditions. Eight adverse events (AEs) were reported in 6 patients. All AEs were mild in severity and resolved. CONCLUSIONS: Tolcapone was able to cross the blood brain-barrier, highlighting its potential to decrease CNS manifestations of ATTRv amyloidosis. Tolcapone was well tolerated by patients with ATTRv amyloidosis.

A case of encephalitis following COVID-19 vaccine.

We describe the first case of encephalitis following coronavirus disease 2019 (COVID-19) vaccination. Our patient was a 46-year-old Japanese woman who presented with acute onset diplopia. Subsequent magnetic resonance imaging revealed brain stem encephalitis that was rapidly responsive to high dosage steroid therapy and completely improved. Although the occurrence of encephalitis after vaccination could have just been a casual temporal association, her symptoms were temporally correlated with two vaccinations. Our case suggests caution and indicates treatment and prognosis, despite no evidence of a causal relationship. Nonetheless, this report emphasizes the enormous benefits of vaccination, which should not be undermined.

Taste disorder in facial onset sensory and motor neuronopathy: a case report.

BACKGROUND: Taste disorder is a common symptom in the general population. Several studies have shown that patients with neurological disorders, such as amyotrophic lateral sclerosis and Parkinson's disease, develop taste disturbance. Facial onset sensory and motor neuronopathy (FOSMN) is a rare disease characterized by sensory disturbance and weakness spreading from the face to the limbs caudally. We describe a patient with FOSMN who showed taste disorder as the sole initial symptom. CASE PRESENTATION: A 49-year-old man who smoked cigarettes developed taste disturbance. Despite using zinc supplements, an herbal medication, and an ointment, his taste disorder worsened. 4 years later, a tingling feeling emerged at the tip of his tongue and gradually spread to his entire lips. At 55 years of age, he showed difficulty in swallowing, followed by facial paresthesia, muscle atrophy, and weakness in the face and upper limbs without apparent upper motor neuron sign. Cessation of smoking did not improve his taste disturbance, and he was unable to discriminate different tastes on the entire tongue. In an electrogustometric study, electrical stimulation did not induce any type of taste sensation. Blink reflex showed delayed or diminished R2 responses. Needle electromyography revealed severe chronic neurogenic changes in the tongue and masseter muscles. Mild chronic neurogenic changes were also observed in the limbs. In the thoracic paraspinal muscles, active neurogenic changes were detected. Findings of hematological and cerebrospinal fluid analyses, and magnetic resonance images of the brain and spinal cord were unremarkable. One cycle of intravenous immunoglobulin therapy did not improve his symptoms. We diagnosed him as having FOSMN with the sole initial symptom of taste disorder. Nine years after the onset of taste disorder, he developed impaired sensation of touch in the right upper limb and required tube feeding and ventilator support. CONCLUSION: Taste disorder can be the initial manifestation of FOSMN and might involve the solitary nucleus.

Length-dependent truncal Aδ-fiber dysfunction in hereditary transthyretin amyloidosis: An intra-epidermal electrical stimulation study.

OBJECTIVE: To elucidate Aδ-fiber dysfunction at the trunk in patients with hereditary transthyretin (ATTRm) amyloidosis using intra-epidermal electrical stimulation (IES). METHODS: In 16 patients with ATTRm amyloidosis and 18 healthy subjects, sensory thresholds using IES and cooling detection thresholds using the Computer-Aided Sensory Evaluation (CASE IV) system, were assessed to investigate Aδ-fiber functions at the Th10 level of the anterior, lateral, and posterior trunk. Furthermore, evoked potentials (EPs) following electrical stimulation using IES at the anterior and posterior trunk were evaluated. RESULTS: In patients with ATTRm amyloidosis, both IES and CASE IV sensory thresholds tended to be higher at the anterior trunk than at the lateral and posterior trunks. The amplitudes of EPs following electrical stimulation at the anterior trunk were lower than those at the posterior trunk. Aδ-fiber dysfunction at the anterior trunk was conspicuous in patients with more intense polyneuropathy at the limbs. In healthy subjects, there were no differences in both sensory thresholds and EP amplitudes among any examination sites. Sensory thresholds with IES and CASE IV were correlated. CONCLUSIONS: Evaluation using IES demonstrated length-dependent Aδ-fiber dysfunction at the trunk in patients with ATTRm amyloidosis. SIGNIFICANCE: IES may be a useful clinical tool for investigating Aδ-fiber dysfunction at various parts of the body in patients with neuropathy.

Electrophysiological demyelinating features in hereditary ATTR amyloidosis.

OBJECTIVE: To elucidate the electrophysiological demyelinating features in patients with hereditary ATTR amyloidosis that may lead to a misdiagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: In 102 patients with hereditary ATTR amyloidosis (85 Val30Met and 17 non-Val30Met; 37 and 65 from endemic and non-endemic areas, respectively), results of motor nerve conduction studies (MNCSs) with a 2-Hz low-cut filter in the unilateral ulnar and tibial nerves were retrospectively investigated to assess whether each MNCS parameter demonstrated demyelinating features that fulfil the European Federation of Neurological Societies/Peripheral Nerve Society electrodiagnostic (EFNS/PNS EDX) criteria for CIDP. RESULTS: Thirteen patients with low compound muscle action potential (CMAP) amplitude in the tibial nerve (0.7 ± 0.7 mV) and prolonged distal CMAP duration in the ulnar nerve satisfied the definite EFNS/PNS EDX criteria for CIDP. Abnormal temporal dispersion and prolongation of distal latency in the tibial nerve were observed in 5 of 13 patients. However, only one of the 13 patients presented with the reduction of motor conduction velocity in each nerve. No patient exhibited conduction block in any nerve. CONCLUSION: Patients with hereditary ATTR amyloidosis occasionally show electrophysiological demyelinating features without conduction block following severe axonal degeneration.

Synthesis of Sterically Fixed Phytochrome Chromophore Derivatives Bearing a 15 E- Fixed or 15 E- Anti- Fixed CD-Ring Component.

To analyze the structure and function of phytochrome chromophores, we have been synthesizing natural and unnatural bilin chromophores of phytochromes. In this manuscript, we report the synthesis of sterically fixed 15 E- fixed 18Et-biliverdin (BV) and 15 E- anti-fixed 18Et-BV derivatives. The key reaction is the introduction of an sp3 carbon alkyl chain bearing a leaving group at the meso-position of the CD-ring component by using the corresponding Grignard reagents in the presence of LiCl.

Postpartum Anti-N-methyl-D-aspartate Receptor Encephalitis: A Case Report and Literature Review.

We describe a 24-year-old woman with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis that developed 3 weeks after normal delivery. She was treated with methylprednisolone, intravenous immunoglobulin, and plasmapheresis, in addition to teratoma excision. However, her recovery was slow, and dysmnesia and mental juvenility persisted even two years after onset. To date, five patients with postpartum anti-NMDAR encephalitis have been reported. All of those patients showed psychotic symptoms and were suspected of having postpartum psychosis in the early period of the encephalitis. Changes in hormonal factors, modification of immune tolerance, or retrograde infection of the ovary may be contributing factors for postpartum anti-NMDAR encephalitis.

Hypertrophic Pachymeningitis as an Early Manifestation of Relapsing Polychondritis: Case Report and Review of the Literature.

Neurological involvement in relapsing polychondritis (RP) is relatively rare. We describe the case of an 80-year-old man who presented with hypertrophic pachymeningitis (HP) together with arthritis as the first manifestation of RP. Auricular chondritis, which subsequently determined the diagnosis of RP, occurred a few weeks after the detection of HP. The neurological symptoms, as well as arthritis, were promptly improved by treatment with corticosteroids. It is generally difficult to diagnose RP in the absence of typical cartilaginous involvement; however, the present case suggests that HP may occur as an early clinical manifestation of RP.