Noise Pareidolia Test in Parkinson's Disease and Atypical Parkinsonian Syndromes: A Retrospective Study.

INTRODUCTION: Pareidolias, or visual misperceptions, are a non-motor symptom of Parkinson's disease (PD) with unclear pathophysiology. The noise pareidolia test (NPT) is a tool for screening pareidolias. The usefulness of the NPT in differentiating PD from atypical parkinsonian syndromes (APS) is also unknown. METHODS: We retrospectively investigated 74 patients with PD and 18 patients with APS who took the NPT. Correlations between the number of pareidolic responses, gray matter volume, and cerebral blood flow were also examined in the patients with PD. RESULTS: The median number of pareidolic responses in patients with PD and patients with APS was 0 (interquartile range (IQR): 0-3) and 0 (IQR: 0-1), respectively, and tended to be higher in patients with PD than in those with APS (p = 0.077). It was significantly higher in patients with PD who had hallucinations (2; IQR: 0-9) (p = 0.016). The area under the receiver operating characteristic curve for the number of pareidolic responses in the NPT was 0.62 when used to differentiate PD and APS, and the optimal cutoff number of pareidolic responses was 2/3. Sensitivity and specificity were 25.7% and 100%, respectively. In the PD group, the number of pareidolic responses was correlated with age (r = 0.27; p = 0.021) and the Frontal Assessment Battery (FAB) score (r = -0.34; p = 0.0099). Magnetic resonance imaging showed no significant correlation between the number of pareidolic responses and the volume of focal gray matter. On cerebral hypoperfusion mapping, the left parietal lobe had a significant correlation with the number of pareidolic responses (r = 0.35; p = 0.027). CONCLUSION: The number of pareidolic responses in NPT was suggested to be useful as a red flag to rule out APS in differentiating PD from APS. In PD without dementia, the number of pareidolic responses was associated with reduced blood flow in the left parietal lobe.

Three-year follow-up of rheumatoid meningitis with matrix metalloprotease-9 levels in the serum and cerebrospinal fluid as indicators of disease activity: A case report.

Rheumatoid meningitis (RM) is an extra-articular complication of rheumatoid arthritis (RA). Although reports of RM sine arthritis exist, most patients with this presentation were diagnosed with RA within one year of RM onset. There are no established biomarkers reflecting the disease activity of RM. This case report highlights the elevation of matrix metalloprotease (MMP)-9 levels during the acute phase of RM and decline during remission. Additionally, this is the first case report of RA diagnosed three years after the onset of RM. It is important to further validate the utility of MMP-9 and conduct long-term follow-up of RM sine arthritis.

Japanese Mucuna pruriens (Hasshou beans) Showed Fast-acting and Long-lasting Effects in Parkinson's Disease.

Objective Mucuna pruriens (MP) is a legume whose seeds contain levodopa (LD), which has potential therapeutic effects against Parkinson's disease (PD). However, further research is needed to thoroughly evaluate its efficacy and safety for treating this condition. In this study, we analyzed the pharmacokinetics of MP grown in Japan and investigated its mechanism of action in PD. Methods MP seeds ground after roasting (containing 4.02% LD per MP powder) were used as the reagent and compared with an equivalent LD/carbidopa (CD) preparation. This clinical trial was conducted using a crossover design among PD patients attending our institution. Each patient received a single dose of 100/10 mg LD/CD tablets and 11 g of MP reagent. Results Among the seven patients with PD, MP prolonged the ON time 2-fold compared to LD/CD. The LD concentrations after MP intake were higher than those after LD/CD intake, whereas dyskinesia did not increase. An analysis of the LD metabolites showed that the 3-O-methyl-dopa/LD metabolic ratio was significantly lower after MP ingestion than after LD/CD ingestion, indicating that MP has a catechol-O-methyl transferase inhibitory effect. Conclusions This is the first report of a pharmacokinetic analysis conducted on actual patients with PD showing that MP significantly prolongs the ON time. The advantages of MP as a treatment for PD have been confirmed: it is inexpensive, as effective as LD, works faster and longer than LD, and does not increase dyskinesia.

Recovery of cardiac metabolic function after high-dose prednisolone in a patient with inflammatory myopathy associated with anti-mitochondrial antibody.

Myocardial complications in the setting of inflammatory myopathy associated with anti-mitochondrial antibody (AMA) cause various cardiovascular complications. A 64-year-old Japanese man was diagnosed with inflammatory myopathy associated with AMA, and three years after diagnosis, the patient was referred to our hospital with leg edema and dyspnea on exertion. Right ventricular endomyocardial biopsy showed no disease-specific findings, with neither inflammatory cell infiltration nor non-caseating epithelioid cell granuloma, and only mild fibrosis; therefore, we finally diagnosed this patient with cardiac involvement in inflammatory myopathy associated with AMA. 123I-ß-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) cardiac scintigraphy showed decreased uptake in wider areas discordant with late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR). One month after starting prednisolone (PSL), the symptoms of congestive heart failure and left ventricular (LV) systolic function had improved. Additionally, BMIPP uptake in the LV myocardium significantly improved compared to that before PSL administration, although decreased BMIPP uptake remained in areas concordant with LGE on CMR. Moreover, it is suggested that recovery of cardiac metabolic function after high-dose PSL administration, which was confirmed through improvement in BMIPP uptake in the LV myocardium, may have led to the improvement in both LV systolic function and heart failure. Learning objective: Although the definitive diagnosis of cardiac involvement in inflammatory myopathy associated with anti-mitochondrial antibody is difficult because of the rarity of this condition and no disease-specific findings in imaging and histology, physicians should consider this in patients with cardiac dysfunction and muscle weakness. 123I-ß-methyl-p-iodophenyl-pentadecanoic acid scintigraphy should be used to assess cardiac metabolic function and treatment efficacy and should be considered for patient management.

Effect of istradefylline on postural abnormalities in patients with Parkinson's disease: An association study of baseline postural angle measurements with changes in Unified Dystonia Rating Scale total score.

In our previous study, istradefylline treatment in patients with Parkinson's disease (PD) improved postural abnormalities (PAs), as seen from a decrease in the mean Unified Dystonia Rating Scale (UDRS) total score from week 0 to week 24. A subgroup analysis based on baseline clinical characteristics investigated the association between improvement in the UDRS total score and istradefylline treatment. However, the association between an objective assessment of PAs and improvement in the UDRS total score is unclear. This ad hoc analysis investigated the association between improvement in the UDRS total score after istradefylline treatment and baseline trunk and neck angles, objective assessments of PAs, measured from patients' photographs taken in the previous study. The patients (n = 31) were stratified into groups based on the trunk forward flexion angle (TFFA), trunk lateral flexion angle (TLFA), and neck flexion angle (NFA) values at baseline. From week 0 to week 24, significant improvements in the UDRS total score were found in median percent change (-8.33% [interquartile range: -43.97, 0.00], P = 0.039) in patients with equal to or above the median TFFA values, and in median change (-|1.50 [-9.25, 0.00], P = 0.015) and median percent change (-13.33% [-50.47, 0.00], P = 0.009) in patients with equal to or above the median TLFA values. Patients with more advanced PAs showed more consistent improvements in the UDRS total score with istradefylline. Baseline TFFA and TLFA values, which are objective values, may be useful to assess the istradefylline effectiveness in patients with PD and PAs.

Predictive value of the neutrophil-to-lymphocyte ratio for treatment response in patients diagnosed with definite or probable autoimmune encephalitis/encephalopathy.

Introduction: Autoimmune encephalitis/encephalopathy (AE) is a complex and heterogeneous disease, making it difficult to predict the prognosis. The neutrophil-to-lymphocyte ratio (NLR) has emerged as a potential prognostic tool, but its usefulness remains a matter of debate. This study aimed to explore prognostic factors in cases of clinically definite or probable AE, including those with autoantibody-negative, or unknown status. Methods: Data on patients diagnosed with definite or probable AE, including those with autoantibody-negative, or unknown status, were retrospectively collected from the admission records of our department between January 2013 and December 2022. These patients were then categorized into either a good- or poor-response group, based on their short-term treatment response. Clinical characteristics, auxiliary examinations, and treatments were compared between the two groups. A multivariable logistic regression model was constructed to identify independent predictors of poor short-term treatment response by Akaike information criterion backward stepwise method. Results: A total of 31 patients were included in the final analysis, with 18 of them included in the poor-response group. In the univariable analysis, the poor-response group had a higher proportion of patients with a modified Rankin Scale (mRS) high score upon admission, female, epileptic seizures, or NLRs of 3.93 or higher than the good-response group (all p < 0.10). Furthermore, the multivariable logistic regression analysis revealed that the mRS score upon admission [OR: 5.51, 95% confidence intervals (CI): 1.29-23.50, p = 0.02], epileptic seizures (OR: 10.01, 95% CI: 1.16-86.66, p = 0.04), and NLRs of 3.93 or higher (OR: 11.37, 95% CI: 1.12-114.68, p = 0.04) were significantly associated with poor short-term treatment response. Conclusion: The NLR may play a supplementary role in predicting the short-term treatment response in patients diagnosed with definite or probable AE, including those with autoantibody-negative, or unknown status.

Characteristics of Guillain-Barré syndrome in super-elderly individuals.

BACKGROUND: Japan has the world's largest super-aging population, and the number of elderly patients with various diseases is increasing. Herein, we reported the characteristics of super-elderly patients, aged over 80 years, with Guillain-Barré syndrome (GBS), a typical neuroimmune disease. METHODS: During the period 2019-2021, 74 patients over the age of 80 years diagnosed with GBS at Kindai university were analyzed as the super-elderly group patients. The control group comprised 74 consecutive patients aged < 79 years, under the same conditions. GBS was diagnosed using Brighton diagnostic criteria. Electrophysiology was assessed using the Ho criteria. RESULTS: The mean age was 83.5 years in the super-elderly group and 51.7 years in the control group. Prior infection was recognized in 50% of cases in the super-elderly group and 77% of cases in the control group with fewer cases in the super-elderly group. The mean number of days until peak symptom presentation was longer in the super-elderly group. The percentage who required a ventilator was significantly higher among the super-elderly group than among the control group. Hughes functional grading scale was more severe in the super-elderly group. Electrophysiological examination revealed the demyelinating form was particularly common in the super-elderly group. Intravenous immunoglobulin was the most common treatment in both the groups, with no difference in efficacy. CONCLUSIONS: Super-elderly onset GBS tends to be severe, therefore it is important to diagnose and treat appropriately, even in the absence of prior episodes of infection.

Diagnostic utility of susceptibility-weighted imaging in amyotrophic lateral sclerosis.

Susceptibility-weighted imaging (SWI) was developed as a diagnostic tool for amyotrophic lateral sclerosis (ALS). However, its sensitivity and specificity are insufficient for accurate diagnosis. Herein, we investigated a new, simple evaluation method for SWI as a diagnostic marker for ALS. We retrospectively investigated 36 patients with ALS and 19 healthy controls. The low signal intensity was semi-quantitatively evaluated on SWI using the motor cortex low intensity (MCLI) score: the sum score of the visual evaluation for the signal intensity of the bilateral primary motor cortices (orofacial, upper-limb, and lower-limb regions) from 0 (isointense) to 2 (markedly hypointense) with a total of 12 points. The mean MCLI score of two independent raters was significantly higher in ALS (median [interquartile range]; 5 [4-6]) than in controls (0 [0-1]), p < 0.0001. When the cutoff value of the MCLI score was set to 3, the area under the receiver operating characteristic curve was 0.973, and the sensitivity and specificity were 0.92 and 1.00, respectively. The MCLI score was not significantly correlated with age, disease duration, and ALS functional rating scale-revised (FRS-R), but was significantly correlated with the progression rate (∆FRS) (ρ = 0.39, p = 0.021) and upper motor neuron score (ρ = 0.51, p = 0.0014). Therefore, MCLI scoring is a useful diagnostic marker for ALS as the MCLI score was correlated with the UMN and ∆FRS scores.

Comparison of two families with and without ataxia harboring novel variants in PRKCG.

Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant SCA caused by variants of the PRKCG encoding protein kinase C gamma (PKCγ). Although the toxic gain-of-function mechanism is the main cause of SCA14, its molecular pathophysiology remains unclear. To elucidate the molecular pathogenesis of SCA14, we analyzed two families with the variants in PRKCG. Clinical symptoms and neurological findings of two Japanese families were evaluated by neurologists. Exome sequencing was performed using the BGI platform. GFP-tagged PRKCGs harboring the identified variants were transfected into the HeLa cells, and aggregation of PKCγ was analyzed using confocal laser microscopy. Solubility of PKCγ was evaluated by assessing the proportion of insoluble fraction present in1% Triton-X. Patients in family 1 presented with only cerebellar atrophy without ataxia; however, patients in family 2 exhibited cerebellar ataxia, dystonia, and more severe cerebellar atrophy than those in family 1. Exome sequencing identified two novel missense variants of PRKCG:c.171 G > C,p.W57C (family 1), and c.400 T > C,p.C134R (family 2). Both the mutant PKCγ aggregated in the cytoplasm. Although the solubility of PKCγ of the C134R variant was lower than that of the wild-type, PKCγ of W57C retained its solubility. In conclusion, we identified two novel variants of PRKCG. The difference in severity between the two families may be due to the difference in solubility changes observed between the two variants. Decreased solubility of the PKCγ may play an important role in the pathogenesis of SCA14.

Probable progressive supranuclear palsy in a patient with chronic schizophrenia: A case report.

Rare neurodegenerative disorders may be considered in the differential diagnosis of Parkinsonism in patients with schizophrenia who show worsening signs of Parkinsonism under treatment with antipsychotics. To the best of our knowledge, the present study is the first report describing probable progressive supranuclear palsy (PSP) in a patient with chronic schizophrenia. A 64-year-old man presented with hallucinations, delusions and asociality. He had received treatment with both typical and atypical antipsychotics for ~13 years. He began experiencing short-term memory impairment and bradykinesia two years before presentation, and then showed increased dysphagia, upper-limb muscle rigidity, extrapyramidal symptoms, vision loss and photophobia. Psychological manifestations included chronic depression, irritability and, occasionally, euphoria. His gait worsened, leading to repeated falls. Antipsychotics were discontinued, and the patient was almost completely dependent on a wheelchair in daily life. In a neurology consultation, he was diagnosed with probable progressive supranuclear palsy-Richardson's syndrome presenting as vertical supranuclear gaze palsy and prominent postural instability with falls. Brain magnetic resonance imaging (MRI) revealed atrophy of the mesencephalic tegmentum, and 123I-ioflupane single-photon emission computed tomography (SPECT) revealed reduced bilateral striatal reuptake. Overall, PSP should be considered in patients with schizophrenia with worsening Parkinsonism, especially when it is accompanied by supranuclear ophthalmoplegia, pseudobulbar palsy, dysarthria and dystonic stiffness of the neck and upper body. In the present case, the combination of brain MRI and 123I-ioflupane SPECT helped to discriminate PSP from other Parkinsonian syndromes, including drug-induced Parkinsonism, in the differential diagnosis.

A single-arm open-label pilot study of brief mindfulness meditation to control impulsivity in Parkinson's disease.

BACKGROUND: Impulse control disorders are detrimental neuropsychiatric symptoms of Parkinson's disease. Increased impulsivity is a predisposing factor for impulse control disorders and should therefore be controlled. Recently, mindfulness meditation as a non-drug therapy has been reported to be useful in improving neuropsychiatric symptoms, such as impulsivity. METHODS: We performed a prospective single-arm, open-label pilot trial to investigate the effectiveness of mindfulness meditation to control impulsivity in patients with Parkinson's disease (UMIN clinical trials registry: UMIN000037779). RESULTS: Twenty patients with Parkinson's disease were enrolled in an 8-week mindfulness meditation program. As a primary outcome, we investigated whether the score of the Barratt Impulsiveness Scale (BIS-11) was significantly reduced after the intervention. As an exploratory examination, functional connectivity changes were also assessed by resting-state functional magnetic resonance imaging. After the intervention, the BIS-11 score was decreased from 59.5 [55.6, 63.3] (mean [95% confidence interval]) to 55.2 [50.3, 60.1] (ΔBIS-11: -4.2, [-7.5, -0.9]). Functional connectivity was increased in the default mode network (DMN) at a cluster including the precuneus, posterior cingulate gyrus, and left posterior lobe (false discovery rate-adjusted p [FDR-p] = 0.046) and in the right frontoparietal network (FPN) at the medial frontal lobe (FDR-p = 0.039). CONCLUSIONS: This open-label, single-arm pilot study provided preliminary data for mindfulness meditation to control the impulsivity of patients with PD. A brief mindfulness meditation program may be effective in controlling impulsivity in PD and may change the functional connectivity of the DMN and right FPN.

Validation of the Japanese Version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS).

Introduction: The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (PD)-Rating Scale (QUIP-RS) was developed to assess the severity of impulsive and compulsive behaviors (ICBs) in PD. We aimed to validate the Japanese version of QUIP-RS and determine the characteristics of ICBs in Japan. Methods: We translated the QUIP-RS into Japanese, back-translated it to English, and obtained confirmation from the original author that the questionnaire remained appropriate. The participants for the validation study were 161 PD patients, identified by continuous sampling at two institutions, who were diagnosed with ICBs through a semistructured interview and completed the QUIP-RS-J. Sensitivity, specificity, and cutoff values were calculated using receiver operating characteristic (ROC) curves. Interinstitutional reliability and test-retest reliability were also assessed for a subset of participants. Results: Twenty-six (16.1%) participants were diagnosed with ICB. The optimal cutoff value of the QUIP-RS-J total score was 6, with area under the curve (AUC) = 0.889 and sensitivity/specificity of 0.92/0.71. Each subscale also showed high AUC (0.89-1.00), sensitivity (0.92-1.00), and specificity (0.71-1.00). Compared with the English version, the optimal cutoff point for binge eating was higher and hypersexuality lower. The total score tended to be higher when described by an informant. Conclusion: The present study validated the Japanese version of QUIP-RS. Use of QUIP-RS-J enables standardized assessment of ICBs and can be used in clinical research, including international multicenter studies.

Schizophrenia after remission of anti-NMDA receptor encephalitis.

N-methyl-D-aspartate receptor (NMDAR) dysfunction is an attractive hypothesis regarding the etiology of schizophrenia. We present the unprecedented case of a woman diagnosed with schizophrenia without anti-NMDAR antibodies after history of NMDAR encephalitis. A first episode of psychosis was antibody-positive and was improved with steroid and immunoglobulin treatment. Second and third episodes were antibody-negative, each about three months postpartum (different pregnancies) and were improved with antipsychotics. Without NMDAR encephalitis-related findings, we diagnosed schizophrenia. After anti-NMDAR encephalitis, NMDAR dysfunction may decrease the threshold for the onset of psychosis. This case provides insight into NMDAR dysfunction on etiology of schizophrenia.

Efficacy and safety of istradefylline in patients with Parkinson's disease presenting with postural abnormalities: Results from a multicenter, prospective, and open-label exploratory study in Japan.

Postural abnormalities in Parkinson's disease (PD) can devastatingly impair the quality of life, especially in patients with advanced disease, and are generally refractory to dopaminergic agents. The objective of this exploratory study was to investigate the efficacy and safety of istradefylline for the treatment of postural abnormalities in PD. In this open-label, 24-week, single-arm prospective trial, PD patients with postural abnormalities experiencing the wearing-off phenomenon on levodopa-containing therapies were enrolled and received a starting dose of 20 mg/day istradefylline orally for 4 weeks, which was then increased to 40 mg/day. The primary endpoint was the change from baseline to week 24 in the 14-item Unified Dystonia Rating Scale (UDRS) total score. Pivotal secondary endpoints were changes in the sub-items of UDRS, Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III, and adverse drug reactions (ADRs). Overall, 24/31 enrolled patients completed the study; mean (standard deviation) age and duration of motor complications were 73.3 (7.7) years and 3.2 (4.4) years, respectively. Mean (95% confidence interval [CI]) change in the UDRS total score was 4.84 (1.97, 7.71; P = 0.002), with significant improvements in the neck, right distal arm and hand, and trunk severity scores. Mean (95% CI) change in the MDS-UPDRS part III score was 7.84 (4.34, 11.34; P < 0.001). The most common ADRs were malaise, dyskinesia exacerbation, and visual hallucinations in 2 (6.5%) patients each. This exploratory study demonstrated that istradefylline could be efficacious for postural abnormalities and was generally well tolerated in patients with PD experiencing the wearing-off phenomenon with levodopa-containing therapies.

Primary phlebitis of central nervous system revealed by black-blood magnetic resonance imaging.

Primary phlebitis of the central nervous system (PPCNS) is a rare condition that might be a subset of primary angiitis of the CNS. In this case report, the patient was a 39-year-old man with a 2-week history of anterograde amnesia and abnormal behaviours. Black-blood MRI (BB-MRI) showed contrast enhancement of the left basilar vein and cerebral superficial veins. Angiography showed unremarkable change in arteries. After a thorough differential diagnosis, we diagnosed PPCNS and then administered methylprednisolone pulse and cyclophosphamide pulse. The neuropsychological symptoms and MRI findings gradually improved, and after 2 months, the dose of prednisolone was gradually reduced to 20 mg. No recurrence was observed. This case shows that BB-MRI may be useful for diagnosing PPCNS.

Neurosarcoidosis Mimicking the Recurrence of Malignant Lymphoma.

A 67-year-old woman with a recurrent history of malignant lymphoma (ML) presented with muscle weakness and paresthesia of the fingertips and feet. Due to the elevated level of serum soluble interleukin-2 receptor and increased 18F-fluorodeoxyglucose uptake in a mediastinal lymph node, neurolymphomatosis was initially suspected. Neurological and electrophysiological examinations were consistent with mononeuropathy multiplex. A diagnosis of neurosarcoidosis was made based on the presence of noncaseating epithelioid granulomas in the mediastinal lymph node, along with the presence of the uveitis, cardiac inflammation, and mononeuropathy multiplex. She was treated with glucocorticoids and azathioprine, and her symptoms disappeared. Sarcoidosis following ML is rare, and since biopsy of nervous systems is often improbable, differentiating neurosarcoidosis and neurolymphomatosis can be difficult as their clinical symptoms can be similar. Clinicians should consider systemic pathological investigations based on 18F-fluorodeoxyglucose positron emission tomography examination in addition to comprehensive evaluation to accurately diagnose neurosarcoidosis.

[Acute-onset autoimmune autonomic ganglionopathy remarkably effective in intravenous high-dose immunoglobulin therapy].

A 77-year-old woman developed acute onset of orthostatic hypotension, urinary retention, and constipation. Neurological examination on admission showed severe orthostatic hypotension accompanied by syncope, mydriatic pupils, and attenuation of light reflexes with no abnormalities in other neurological systems. Autonomic testing revealed denervation hypersensitivity in norepinephrine (NE) intravenous infusion test and 0.125% pilocarpine instillation test, low NE in the serum, and decreased amount of sweating in quantitative sudomotor axon reflex test. These findings indicated dysfunction of postganglionic autonomic nerves. Autoimmune autonomic ganglionopathy (AAG) was diagnosed due to the presence of anti-ganglionic acetylcholine receptors. The patient was given intravenous high-dose immunoglobulin therapy (IVIg), improving orthostatic hypotension, urinary retention, and constipation. Previous reports indicated that the response to IVIg varied from case to case. Thus, this case suggests that IVIg is effective in acute-onset AAG cases.