Two distinct degenerative types of nigrostriatal dopaminergic neuron in the early stage of parkinsonian disorders.

Introduction: The present study characterized the degeneration of nigrostriatal dopaminergic neurons in the early stages of parkinsonian disorders using integrative neuroimaging analysis with neuromelanin-sensitive MRI and 123I-FP-CIT dopamine transporter (DAT) SPECT. Methods: Thirty-one, 30, and 29 patients with progressive supranuclear palsy (PSP), corticobasal syndrome (CBS) with abnormal specific binding ratio (SBR) in either hemisphere (mean ± 2SD), and parkinsonism-predominant multiple system atrophy (MSA-P), respectively, were enrolled. Neuromelanin-related contrast (NRC) in the substantia nigra (NRCSN) and locus coeruleus (NRCLC) and the SBR of DAT SPECT were measured. All the patients underwent both examinations simultaneously within five years after symptom onset. After adjusting for interhemispheric asymmetry on neuromelanin-related MRI contrast using the Z-score, linear regression analysis of the NRCSN and SBR was performed for the most- and least-affected hemispheres, as defined by the interhemispheric differences per variable (SBR, NRCSN, standardized [SBR + NRCSN]) in each patient. Results: Although the variables did not differ significantly between PSP and CBS, a significant correlation was found for CBS in the most-affected hemisphere for all the definitions, including the clinically defined, most-affected hemisphere. No significant correlation was found between the NRCSN and SBR for any of the definitions in either PSP or MSA-P. Conclusion: Together with the findings of our previous study of dementia with Lewy bodies (DLB) and Parkinson's disease (PD), the present findings indicated that neural degeneration in the disorders examined may be categorized by the significance of the NRCSN-SBR correlation in PD and CBS and its non-significance in DLB, PSP, and MSA-P.

[MR neurography reveals fascicular constriction of the median nerve in a patient with neuralgic amyotrophy].

Diagnosing neuralgic amyotrophy can be challenging in clinical practice. Here, we report the case of a 37-years old Japanese woman who suddenly developed neuropathic pain in the right upper limb after influenza vaccination. The pain, especially at night, was severe and unrelenting, which disturbed her sleep. However, X-ray and MRI did not reveal any fractures or muscle injuries, and brain MRI did not reveal any abnormalities. During neurological consultation, she was in a posture of flexion at the elbow and adduction at the shoulder. Manual muscle testing suggested weakness of the flexor pollicis longus, pronator quadratus, flexor carpi radialis (FCR), and pronator teres (PT), while the flexor digitorum profundus was intact. Medical history and neurological examination suggested neuralgic amyotrophy, particularly anterior interosseous nerve syndrome (AINS) with PT/FCR involvement. Innervation patterns on muscle MRI were compatible with the clinical findings. Conservative treatment with pain medication and oral corticosteroids relieved the pain to minimum discomfort, whereas weakness remained for approximately 3 months. For surgical exploration, lesions above the elbow and fascicles of the median nerve before branching to the PT/FCR were indicated on neurological examinations; thus, we performed high-resolution imaging to detect possible pathognomonic fascicular constrictions. While fascicular constrictions were not evident on ultrasonography, MR neurography indicated fascicular constriction proximal to the elbow joint line, of which the medial topographical regions of the median nerve were abnormally enlarged and showed marked hyperintensity on short-tau inversion recovery. In patients with AINS, when spontaneous regeneration cannot be expected, timely surgical exploration should be considered for a good outcome. In our case, MR neurography was a useful modality for assessing fascicular constrictions when the imaging protocols were appropriately optimized based on clinical assessment.

Degeneration of nigrostriatal dopaminergic neurons in the early to intermediate stage of dementia with Lewy bodies and Parkinson's disease.

OBJECTIVE: To investigate differences in nigrostriatal dopaminergic neuron degeneration between dementia with Lewy bodies (DLB) and Parkinson's disease (PD) in the early to intermediate stage of these diseases. METHODS: An integrative neuroimaging analysis was developed using 3-Tesla neuromelanin-sensitive MRI and 123I-FP-CIT dopamine transporter SPECT, and the relationship and laterality of three variables, including neuromelanin-related contrast in the substantia nigra (NRCSN) and locus coeruleus (NRCLC) and the specific binding ratio (SBR) in the striatum, were examined in detail. Patients with DLB and PD and control subjects (n = 29, 52, and 18, respectively) were enrolled. RESULTS: A significantly greater decrease in the SBR in the bilateral hemispheres was observed in DLB than in PD. After adjusting for the interhemispheric asymmetry in neuromelanin-related MRI contrast by using the Z-score, linear regression between the NRCSN and SBR was performed for the most-affected/least-affected sides of the hemispheres as defined by the interhemispheric differences in each variable (SBR, NRCSN, standardized [SBR + NRCSN]). In DLB, the highest, albeit statistically non-significant, correlation was observed in the SBR-based, most-affected side. In PD, the highest correlation was observed in the (SBR + NRCSN)-based, most-affected side, which approximated the value of the clinically-defined, most-affected side. A non-significant correlation was observed only in the (SBR + NRCSN)-based or clinically-defined, least-affected side. CONCLUSION: Loss of the soma and presynaptic terminals may occur independently in DLB with a large decrease in the presynaptic terminals. The close relationship observed between the degeneration of the soma and presynaptic terminals suggested that axon degeneration may dominate in PD.

Novel partial deletions, frameshift and missense mutations of CSF1R in patents with CSF1R-related leukoencephalopathy.

BACKGROUND AND PURPOSE: Colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is an adult-onset leukoencephalopathy caused by mutations in CSF1R. The present study aimed to explore the broader genetic spectrum of CSF1R-related leukoencephalopathy in association with clinical and imaging features. METHODS: Mutational analysis of CSF1R was performed for 100 consecutive patients with adult-onset leukoencephalopathy. Sequence and copy number variation (CNV) analyses of CSF1R were performed. The genomic ranges of the deletions were determined by long-read sequencing. Ligand-dependent autophosphorylation of CSF1R was examined in cells expressing the CSF1R mutants identified in this study. RESULTS: CSF1R mutations were identified in 15 patients, accounting for 15% of the adult-onset leukoencephalopathy cases. Seven novel and five previously reported CSF1R mutations were identified. The novel mutations, including three missense and one in-frame 3 bp deletion, were located in the tyrosine kinase domain (TKD) of CSF1R. Functional assays revealed that none of the novel mutations in the TKD showed autophosphorylation of CSF1R. Two partial deletions of CSF1R were identified that resulted in lack of the C-terminal region, including the distal TKD, in two patients. Various clinical features including cognitive impairment, psychiatric symptoms and gait disturbance were observed. Various degrees of the white matter lesions and corpus callosum abnormalities on magnetic resonance imaging and characteristic calcifications on computed tomography were observed as imaging features. CONCLUSIONS: Our results highlight the importance of examining the CNV of CSF1R even when Sanger or exome sequencing reveals no CSF1R mutations. Genetic examination of sequences and CNV analyses of CSF1R are recommended for an accurate diagnosis of CSF1R-related leukoencephalopathy.

[Functional (Psychogenic) Movement Disorder Focusing on Involuntary Movements: A Review].

Functional neurological disorders differ from malingering/factitious disorders and are diagnosed based solely on careful history taking and neurological evaluation. Some clinical characteristics, including distractibility, entrainability, and variability are important to identify the positive physical signs that indicate functional alterations. Thorough investigations are not essential to exclude organic pathologies, whereas electrophysiological and radiological findings are sometimes useful. Neurologists play an important role when they explain the diagnosis to the patient. The explanation itself may be therapeutic, when delivered successfully and may help patients to understand the nature and mechanisms underlying their movement disorder. A multidisciplinary team approach, including coordination between rehabilitation therapists and psychotherapists may produce positive treatment outcomes, particularly in movement disorder centers. In this article, we discuss some functional neurological disorders, including those in patients with functional movement disorders (involuntary movements) together with video presentations.

Leucine-rich Glioma-inactivated 1 Encephalitis Followed by Isaacs Syndrome: Alternating Presence of Pathogenic Autoantibodies to Leucine-rich Glioma-inactivated 1 and Contactin-associated Protein-like 2.

The coexistence of leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) autoantibodies in the same individual is surprisingly often observed. We herein report the first case of LGI1 encephalitis followed by Isaacs syndrome in which LGI1 and CASPR2 antibodies in the serum and cerebrospinal fluid (CSF) were measured during the entire disease course. After the resolution of limbic encephalitis, LGI1 antibodies disappeared from the CSF simultaneously with the appearance of CASPR2 antibodies in the serum. The alternating presence of these pathogenic autoantibodies along with the clinical and phenotypic alternations suggested that LGI1 encephalitis was associated with CASPR2 autoantibody production in the peripheral tissue, leading to CASPR2-associated Isaacs syndrome.

Unique Lewy pathology in myotonic dystrophy type 1.

Lewy body-related α-synucleinopathy (Lewy pathology) has been reported in patients with myotonic dystrophy (DM) type 1 (DM1), but no detailed report has described the prevalence and extent of its occurrence. We studied consecutive full autopsy cases of DM1 at the National Center of Neurology and Psychiatry (NCNP) Brain Bank for intractable psychiatric and neurological disorders. Thirty-two cases, genetically determined to be DM1 (59.0 ± 8.7 years), obtained from the NCNP Brain Bank, were compared with control cases obtained from the Brain Bank for Aging Research (BBAR) in Japan. The investigated anatomical sites followed the Dementia with Lewy Bodies Consensus Guideline, expanding to the peripheral autonomic nervous system, temporal pole, and occipital cortex, in addition to the olfactory epithelium and spinal cord. Of the 32 patients, 11 (34.4%) had Lewy pathology, with a significantly higher prevalence than that in the control cases from the BBAR (20.1%). Lewy pathology detected in DM1 was widespread, but no macroscopic depigmentation of the substantia nigra was observed in any DM1 case; this was commensurate with the microscopic paucity of Lewy pathology in the substantia nigra and amygdala. Lewy pathology in DM1 does not appear to follow either Braak's ascending paradigm or the olfactory-amygdala extension. Lewy neurites and dots in DM1 were very sparse in the cerebral cortex and distinct from those observed in BBAR control cases. This study was the first demonstration of unique Lewy pathology in DM1 and may contribute to the understanding of the protein propagation hypothesis of Lewy pathology.

Myoclonic Epilepsy with Ragged-red Fibers with Intranuclear Inclusions.

We herein report a case of myoclonic epilepsy with ragged-red fibers (MERRF) harboring a novel variant in mitochondrial cysteine transfer RNA (MT-TC). A 68-year-old woman presented with progressive myoclonic epilepsy with optic atrophy and peripheral neuropathy. A skin biopsy revealed p62-positive intranuclear inclusions. No mutations were found in the causative genes for diseases known to be related to intranuclear inclusions; however, a novel variant in MT-TC was found. The association between intranuclear inclusions and this newly identified MERRF-associated variant is unclear; however, the rare complication of intranuclear inclusions in a patient with typical MERRF symptoms should be noted for future studies.

Enlarged high frequency oscillations of the median nerve somatosensory evoked potential and survival in amyotrophic lateral sclerosis.

OBJECTIVE: A large N20 and P25 of the median nerve somatosensory evoked potential (SEP) predicts short survival in amyotrophic lateral sclerosis (ALS). We investigated whether high frequency oscillations (HFOs) over N20 are enlarged and associated with survival in ALS. METHODS: A total of 145 patients with ALS and 57 healthy subjects were studied. We recorded the median nerve SEP and measured the onset-to-peak amplitude of N20 (N20o-p), and peak-to-peak amplitude between N20 and P25 (N20p-P25p). We obtained early and late HFO potentials by filtering SEP between 500 and 1 kHz, and measured the peak-to-peak amplitude. We followed up patients until endpoints (death or tracheostomy) and analyzed the relationship between SEP or HFO amplitudes and survival using a Cox analysis. RESULTS: Patients showed larger N20o-p, N20p-P25p, and early and late HFO amplitudes than the control values. N20p-P25p was associated with survival periods (p = 0.0004), while early and late HFO amplitudes showed no significant association with survival (p = 0.4307, and p = 0.6858, respectively). CONCLUSIONS: The HFO amplitude in ALS is increased, but does not predict survival. SIGNIFICANCE: The enlarged HFOs in ALS might be a compensatory phenomenon to the hyperexcitability of the sensory cortex pyramidal neurons.

Midbrain atrophy related to parkinsonism in a non-coding repeat expansion disorder: five cases of spinocerebellar ataxia type 31 with nigrostriatal dopaminergic dysfunction.

BACKGROUND: Spinocerebellar ataxia type 31 (SCA31) is caused by non-coding pentanucleotide repeat expansions in the BEAN1 gene. Clinically, SCA31 is characterized by late adult-onset, pure cerebellar ataxia. To explore the association between parkinsonism and SCA31, five patients with SCA31 with concomitant nigrostriatal dopaminergic dysfunction (NSDD) development, including three cases of L-DOPA responsive parkinsonism, were analyzed. METHODS: To assess regional brain atrophy, cross-sectional and longitudinal imaging analyses were retrospectively performed using magnetic resonance imaging (MRI) planimetry. The midbrain-to-pons (M/P) area ratio and cerebellar area were measured on midsagittal T1-weighted MRI in five patients with SCA31 with concomitant NSDD (NSDD(+)), 14 patients with SCA31 without NSDD (NSDD(-)), 32 patients with Parkinson's disease (PD), and 15 patients with progressive supranuclear palsy (PSP). Longitudinal changes in the M/P area ratio were assessed by serial MRI of NSDD(+) (n = 5) and NSDD(-) (n = 9). RESULTS: The clinical characteristics assessed in the five patients with NSDD were as follows: the mean age at NSDD onset (72.0 ± 10.8 years), prominence of bradykinesia/akinesia (5/5), rigidity (4/5), tremor (2/5), dysautonomia (0/5), vertical gaze limitation (1/5), and abnormalities on 123I-ioflupane dopamine transporter scintigraphy (3/3) and 3-Tesla neuromelanin MRI (4/4). A clear reduction in the midbrain area and the M/P area ratio was observed in the NSDD(+) group (p < 0.05) while there was no significant difference in disease duration or in the pons area among the NSDD(+), NSDD(-), and PD groups. There was also a significant difference in the midbrain and pons area between NSDD(+) and PSP (p < 0.05). Thus, mild but significant midbrain atrophy was observed in NSDD(+). A faster rate of decline in the midbrain area and the M/P area ratio was evident in NSDD(+) (p < 0.05). CONCLUSION: The clinical characteristics of the five patients with SCA31 with concomitant NSDD, together with the topographical pattern of atrophy, were inconsistent with PD, PSP, and multiple system atrophy, suggesting that SCA31 may manifest NSDD in association with the pathomechanisms underlying SCA31.

Immunoglobulin G4-related Disease Accompanied by Peripheral Neuropathy: A Report of Two Cases.

Due to its rarity and the limited literature, the clinicopathological characteristics of peripheral nerve involvement in immunoglobulin G4 (IgG4)-related disease are unknown. We present two cases of IgG4-related disease, accompanied by peripheral neuropathy, presenting as unilateral ptosis (case 1) and sclerosing cholangitis (case 2), respectively. In both cases, sural nerve biopsy indicated vasculitis as the underlying pathophysiology; the peripheral neuropathy was refractory to corticosteroid therapy. In contrast to the previously proposed pathomechanism of IgG4-related neuropathy (direct lymphoplasmacytic infiltration), the pathological findings in our cases suggest that vasculitis occurs secondary to systemic autoimmune conditions.

Effects of oral care on prolonged viral shedding in coronavirus disease 2019 (COVID-19).

AIM: To assess the effects of oral care on prolonged viral shedding in coronavirus disease 2019 (COVID-19) patients. METHODS AND RESULTS: We evaluated the clinical course of eight COVID-19 patients, including their duration of viral shedding, by PCR testing of nasopharyngeal swabs. The average time from the onset of symptoms until the virus was no longer detectable was 31.6 ± 11.8 days (mean ± SD; range 17-53). Thus, it took 15.1 ± 14.7 (1-40) days from the time of clinical recovery for the virus to become undetectable. In two patients who had mental retardation and psychiatric disorders, the viral shedding period continued for 44 days or 53 days. These two patients did not voluntarily brush their teeth. When they were instructed on the importance of oral care, including tooth brushing and gargling, their tests for the coronavirus became negative. CONCLUSION: Most of the patients with COVID-19 had a viral shedding period of 30 days or less. In cases of prolonged viral shedding (≥44 days), noninfectious viral nucleic acid may have accumulated in uncleaned oral cavities and continued to be detected. We propose that tooth brushing and gargling remove such viral nucleic acid and improve the accuracy of PCR testing.

Lidocaine injections and neck corset wearing improve dropped head syndrome in Parkinson's disease and related disorders.

BACKGROUND: Patients with Parkinson's disease and related disorders (PDRD) may exhibit dropped head syndrome (DHS), which does not yet have an effective treatment. OBJECTIVES: To evaluate the effect of combining lidocaine injection into the bilateral scalene muscles and neck corset wearing on dropped head syndrome. METHODS: We performed needle electromyography assessments of the scalene, sternocleidomastoid (SCM), levator scapulae, splenius capitis, and trapezius muscles. Patients received 2.5-5 ml injections of 1% lidocaine into both sides of the scalene muscles for 4/5 consecutive days and were instructed to wear a neck corset. We measured the neck flexion angle, which formed between the horizontal line and the straight line passing through the ear canal and orbital fossa, before (baseline) and after (Day 8 and Day 90) the intervention. RESULTS: Seven males and eight females (mean age, 68.9 years; range 56 to 85 years) who had PDRD with dropped head syndrome were enrolled in this study. Needle electromyography examination revealed abnormal discharge of the scalene muscles in all patients when the neck position was corrected; however, some patients did not show abnormal discharge of the SCM muscle. At Day 8, we observed an improvement of the neck flexion angle in 13 of the 15 patients, from an average of 27.7°â€¯±â€¯13.9° to 11.7 ±â€¯14.6°. At Day 90, the average neck flexion angle was 15.3°â€¯±â€¯17.2°. CONCLUSIONS: Combining lidocaine injection into the scalene muscles and neck corset wearing is an effective treatment regimen for DHS in patients with PDRD.

Phenotypic variability of Niemann-Pick disease type C including a case with clinically pure schizophrenia: a case report.

BACKGROUND: Niemann-Pick disease type C (NPC) is a lysosomal storage disorder with severe prognosis. Disease-specific therapy is crucial to prevent disease progression; however, diagnosing NPC is quite difficult because of remarkably variable clinical presentations. The NPC Suspicion Index (NPC-SI) was developed to overcome this problem. Identifying preclinical cases is important for prevention and therapy. Here, we report three newly diagnosed NPC cases, one typical juvenile-onset case and the cases of two sisters with symptoms neurologically/psychiatrically indistinguishable from dystonia and schizophrenia, respectively. CASE PRESENTATION: In Case 1, a 25-year-old man presented with a 14-year history of intellectual disability, clumsiness, spastic ataxia, dysphagia, and frequent falls. Neurological examination revealed vertical supranuclear gaze palsy and involuntary movements. Ultrasonography revealed mild splenomegaly, and filipin staining of skin fibroblasts was positive with a variant staining pattern. NPC1 gene analysis showed compound heterozygous mutations, including c.1421C > T (p.P474L), a known causative mutation, and c.3722 T > C (p.L1241S), a new mutation. In Case 2, a 28-year-old woman, the proband, who had marked splenomegaly in her childhood, survived well, contrary to the expected severe prognosis of infantile NPC. She had minor neuropsychiatric symptoms including auditory hallucinations, nocturnal urination, and sleep paralysis. At the age of 28 years, she presented with a 1-year history of orofacial and oromandibular painful dystonia. The patient's 35-year-old sister (Case 3) was diagnosed with schizophrenia. In both cases, filipin staining of skin fibroblasts was positive with variant staining patterns, as well as elevated levels of urinary bile acids. NPC1 gene analysis showed compound heterozygous mutations including c.3011C > T (p.S1004 L), a known causative mutation, and c.160_161insG (p.D54GfsX4), a new mutation. Their mother, who was under therapy with modafinil for narcolepsy, shared the latter mutation. CONCLUSIONS: Marked clinical variability was observed in our three cases. NPC could masquerade as a pure neuropsychiatric disorder such as dystonia or schizophrenia. Abdominal ultrasonography, history evaluation, and neurological examination were quite important in the diagnostic process.

Long-term effect of repeated lidocaine injections into the external oblique for upper camptocormia in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is occasionally complicated by camptocormia. In a previous study, we classified camptocormia into upper and lower types based on the inflection point, and reported that lidocaine injection into the external oblique muscle, but not into the internal oblique or rectus abdomen, improved upper camptocormia in PD. The effect of a single lidocaine injection disappeared over a period of few days. In this study, we used repeated lidocaine injections into the external oblique for 4-5 days and evaluated the effects of such treatment for up to 90 days. METHODS: The study subjects were 12 patients with PD and upper camptocormia who were treated with repeated lidocaine injections into the bilateral external oblique followed by rehabilitation. The effect of treatment was evaluated by measuring the angle of truncal flexion before and after the injection. Patients who showed improvement with repeated injections were evaluated during a 90-day period. RESULTS: Eight out of 12 patients showed significant improvement in posture after a single lidocaine injection. However, the effect subsided several days after treatment. Repeated injections produced long-term improvement in 9 out of 12 patients, which was maintained during the 90-day observation period in eight of these patients. CONCLUSIONS: Our results showed that repeated lidocaine injections into the external oblique improved upper camptocormia, and that the effect was maintained in the majority of patients during the 90-day observation period, indicating that repeated lidocaine injections into the external oblique have therapeutic effect on upper camptocormia in patients with Parkinson's disease.

New-onset type 1 diabetes mellitus and anti-aquaporin-4 antibody positive optic neuritis associated with type 1 interferon therapy for chronic hepatitis C.

A 60-year-old woman developed type 1 diabetes mellitus and anti-aquaporin-4 antibody positive optic neuritis during type 1 interferon therapies for chronic hepatitis C. The diabetes mellitus was elicited by interferon-α plus ribavirin therapy, while the optic neuritis was induced after interferon-ß treatment, followed by interferon-α and ribavirin therapy. It is possible that type 1 interferons lead to the onset of the two autoimmune diseases by inducing disease-specific autoantibodies. Autoimmune disease is an infrequent complication of type 1 interferon treatment; however, once it has occurred, it may result in severe impairments. Patients undergoing type 1 interferon therapy should therefore be carefully monitored for any manifestations of autoimmune diseases.

Potential pathophysiological role of D-amino acid oxidase in schizophrenia: immunohistochemical and in situ hybridization study of the expression in human and rat brain.

D-Amino acid oxidase (DAO) is a peroxisomal flavoenzyme that catalyzes oxidative deamination of a wide range of D-amino acids. Among the possible substrates of DAO in vivo, D-serine is proposed to be a neuromodulator of the N-methyl-D-aspartate (NMDA) type glutamate receptor. The gene for DAO was reported to be associated with schizophrenia. Since DAO is expected to be one of the key enzymes in the regulation of NMDA neurotransmission, the modulation of the enzyme activity is expected to be therapeutical for neuronal disorders. In search of the pathophysiological role of DAO, we analyzed the distribution of DAO mRNA and protein in the rat and human brain. In rat, the distribution of DAO mRNA was newly detected in choroid plexus (CP) epithelial cells in addition to glial cells of pons, medulla oblongata, and especially Bergmann glia of cerebellum. Moreover, to investigate how DAO expression level is altered in schizophrenia, we performed immunohistochemistry in the human brain. In agreement with the results in the rat brain, the immunoreactivity for DAO was detected in glial cells of rhombencephalon and in CP. Furthermore, higher level of DAO expression was observed in schizophrenic CP epithelial cells than that in non-schizophrenic cases. These results suggest that an increase in DAO expression in parts of the brain is involved in aberrant D-amino acid metabolism. In particular, gene expression of DAO in CP suggests that DAO may regulate D-amino acid concentration by modulating the cerebrospinal fluid and may be regarded as a potential therapeutic target for schizophrenia.

Chlorpromazine oligomer is a potentially active substance that inhibits human D-amino acid oxidase, product of a susceptibility gene for schizophrenia.

D-amino acid oxidase (DAO), a potential risk factor for schizophrenia, has been proposed to be involved in the decreased glutamatergic neurotransmission in schizophrenia. Here we show the inhibitory effect of an antipsychotic drug, chlorpromazine, on human DAO, which is consistent with previous reports using porcine DAO, although human DAO was inhibited to a lesser degree (K(i) = 0.7 mM) than porcine DAO. Since chlorpromazine is known to induce phototoxic or photoallergic reactions and also to be transformed into various metabolites, we examined the effects of white light-irradiated chlorpromazine on the enzymatic activity. Analytical methods including high-resolution mass spectrometry revealed that irradiation triggered the oligomerization of chlorpromazine molecules. The oligomerized chlorpromazine showed a mixed type inhibition with inhibition constants of low micromolar range, indicative of enhanced inhibition. Taken together, these results suggest that oligomerized chlorpromazine could act as an active substance that might contribute to the therapeutic effects of this drug.