Recurrent HyperCKemia with Immunological Involvement of the Endomysial Capillaries in Neuromyelitis Optica.

A 55-year-old woman with neuromyelitis optica (NMO) had recurrent myalgias with hyperCKemia. A muscle biopsy suggested nonspecific myopathic changes. Regarding immunohistochemistry, the expression of both major histocompatibility complex class I and myxovirus resistance protein A was observed in the endomysial capillaries, suggesting immunological involvement of these capillaries, whereas both C5b9 (membrane attack complex) and aquaporin 4 immunofluorescence stainings were normal. The present findings led us to conclude that one possible mechanism for hyperCKemia in NMO underlying the immunological involvement of the endomysial capillaries was an as-yet-unidentified factor that triggered damage to the integrity of the sarcolemma and thereby cause CK leakage into the serum.

Nonsystemic vasculitic neuropathy in a patient with IgG-monoclonal gammopathy of undetermined significance: A case report.

RATIONALE: Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell proliferative disorder that consistently precedes multiple myeloma. Peripheral neuropathy in patients with IgG-MGUS tends to vary in clinical phenotype. We report a rare case of a patient with IgG-MGUS who had nonsystemic vasculitic neuropathy (NSVN). PATIENT CONCERNS: A 56-year-old Japanese woman presented with progressive sensory ataxia with episodic paresthesia. Her clinical and laboratory values were compatible with IgG-MGUS. A nerve conduction study suggested possible chronic inflammatory demyelinating polyneuropathy. However, intravenous immunoglobulin therapy was not effective. A sural nerve biopsy specimen revealed mildly reduced myelinated fiber density and myelin ovoid formation, with epineural arterioles infiltrated by inflammatory cells. DIAGNOSES: We accordingly diagnosed her condition as NSVN. INTERVENTIONS: She was accordingly started on oral prednisolone (40 mg/d) at 3 months after the onset of her neurological symptoms. OUTCOMES: At 1 year after the oral prednisolone treatment was begun, the patient's neurological symptoms showed no worsening. LESSONS: These findings indicate NSVN as a possible cause of peripheral neuropathy in patients with IgG-MGUS. Cumulatively, our findings highlight the need for a nerve biopsy for peripheral neuropathy in patients with IgG-MGUS as a possible cause of NSVN. The early diagnosis of NSVN is expected to be beneficial for such patients.

Correlated levels of cerebrospinal fluid pathogenic proteins in drug-naïve Parkinson's disease.

BACKGROUND AND AIM: Toxic oligomeric α-synuclein (αS; O-αS) has been suggested to play a central role in the pathogenesis of Lewy body diseases such as Parkinson's disease (PD). Cerebrospinal fluid (CSF) levels of αS, O-αS, total and phosphorylated tau, and amyloid ß 1-42 (Aß1-42) are thought to reflect the pathophysiology or clinical symptoms in PD. In this study, we examined correlations of the CSF levels of these proteins with the clinical symptoms, and with each other in drug-naïve patients with PD. METHODS: Twenty-seven drug-naïve patients with PD were included. Motor and cognitive functions were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment (MoCA), and Neurobehavioral Cognitive Status Examination (COGNISTAT). CSF levels of total αS, O-αS, Aß1-42, total tau and tau phosphorylated at threonine 181 (P-tau181p) were measured. CSF levels of these proteins were compared with clinical assessments from the UPDRS, MoCA and COGNISTAT using Spearman correlation analysis. Spearman correlation coefficients among CSF protein levels were also evaluated. RESULTS: CSF levels of αS were negatively correlated with UPDRS part III (motor score) (p < 0.05) and bradykinesia (p < 0.01), and positively correlated with COGNISTAT subtest of judgement (p < 0.01) and CSF levels of Aß1-42 (p < 0.001), total tau (p < 0.001) and P-tau181p (p < 0.01). Lower CSF levels of Aß1-42, total tau and P-tau181p were significantly related to worsening of some motor and/or cognitive functions. The CSF level of O-αS showed no correlation with any motor and cognitive assessments or with CSF levels of the other proteins. CONCLUSION: CSF levels of αS are correlated with some clinical symptoms and CSF levels of other pathogenic proteins in drug-naïve PD patients. These correlations suggest a central role for interaction and aggregation of αS with Aß1-42, tau, and phosphorylated tau in the pathogenesis of PD. Although O-αS has been shown to have neurotoxic effects, CSF levels do not reflect clinical symptoms or levels of other proteins in cross-sectional assessment.

Usefulness Differs Between the Visual Assessment and Specific Binding Ratio of 123I-Ioflupane SPECT in Assessing Clinical Symptoms of Drug-Naïve Parkinson's Disease Patients.

Background: In clinical practice, assessment of the striatal accumulation in 123I-ioflupane single photon emission computed tomography (SPECT) is commonly performed calculating the specific binding ratio (SBR) for the whole striatum. On the other hand, visual assessment of striatal accumulation in the SPECT was recently established. However, correlations of visual assessment with motor and cognitive functions in Parkinson's disease (PD) have rarely been examined. Differences in the usefulness of these assessments at clinics are uncertain. Objective: We performed this study to compare correlations of cognitive and motor functions in drug-naive PD between the SBR and visual assessment using 123I-ioflupane SPECT. Methods: Cognitive and motor assessments and 123I-ioflupane SPECT were performed in 47 drug-naïve PD patients with Mini-mental State Examination scores of ≥25. Cognitive function was assessed using the total score and 6 subscores of the Montreal Cognitive Assessment (MoCA) and 10 separate subtests of the Neurobehavioral Cognitive Status Examination (COGNISTAT). Motor function was assessed using the Hoehn and Yahr scale and Unified Parkinson's Disease Rating Scale. Accumulation of 123I-ioflupane was determined by visual assessment based on five grades: 1, burst striatum; 2, egg-shaped; 3, mixed type; 4, eagle wing; 5, normal striatum; and by calculating SBR averaged for the bilateral striatum using the DaTView computer software commonly used in clinical practice. Each SPECT assessment was compared with each subscore for cognitive and motor assessments. Results: Spearman correlation analysis showed SBR was significantly correlated with the MoCA subscores of visuospatial function and attention, and with COGNISTAT subtests of attention. Visual assessment showed significant negative correlation with the Hoehn and Yahr scale. Mean score of postural instability in patients with visual grade of 1 was significantly higher than those in patients with visual grades of 2 and 3. Conclusion: Clinical symptoms reflected by 123I-ioflupane SPECT differ between the SBR and visual assessment. SBR reflects some cognitive functions, whereas a visual assessment grade of 1, which signifies decreased uptake of 123I-Ioflupane in the caudate nucleus, reflects postural instability. Thus, the caudate nucleus may play an important role in posture maintenance. Our results suggest that performing both assessments is of value.

Effects of dopaminergic drug adjustment on executive function in different clinical stages of Parkinson's disease.

BACKGROUND: Effects of dopaminergic medication on executive function in patients with Parkinson's disease (PD) are inconsistent. OBJECTIVE: We examined the effect of dopaminergic medication on executive function in 24 drug-naïve PD patients (de novo group) and in 21 PD patients on chronic dopaminergic medication (chronic medication group). METHODS: PD patients without dementia were included in this study. For the de novo group patients, dopaminergic medication was initiated, and the dose was increased to improve motor symptoms. For the chronic medication group patients, dopaminergic medication was adjusted to relieve clinical problems. All participants were tested prior to and at 4-7 months after the drug initiation/adjustment. Executive function was assessed by using the Behavioral Assessment of the Dysexecutive Syndrome (BADS). Motor function was assessed by using the Unified Parkinson's Disease Rating Scale (UPDRS; part III). Improvement in executive function was compared with a simultaneous change in levodopa equivalent doses (LED) of dopaminergic medication and with improvement in motor functions. RESULTS: The mean standardized BADS scores showed no significant improvement in both the groups. In the de novo group, percent improvement in the standardized BADS scores showed a significant positive correlation with the LED, but not with percent improvement in UPDRS part III. In the chronic medication group, percent improvement in the standardized BADS scores was negatively correlated with change in the LED, but not with percent improvement in UPDRS part III. Multiple regression analysis using improvement in the standardized BADS score as a dependent variable and patient's background factors (ie, age, education, disease duration, and motor and executive assessments at baseline) as independent variable showed that improvement in the executive assessment is significantly correlated with the LED only in the de novo group. CONCLUSION: Effects of dopaminergic drug adjustment on executive function differ according to the patient's clinical stage and depend on LED in de novo stage.

Accumulation of 123I-Ioflupane Is a Useful Marker of the Efficacy of Selegiline Monotherapy in Drug-Naïve Parkinson's Disease.

Background: Selegiline enhances the patient's endogenous dopamine by inhibiting dopamine metabolism. The efficacy of selegiline monotherapy for drug-naïve Parkinson's disease (PD) patients may depend on the degree of dopaminergic neuronal degeneration. 123I-Ioflupane single photon emission computed tomography (SPECT) and 123I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy are diagnostic methods to assess the pharmacological and pathological changes in PD. Objective: We examined the utility of these imaging methods to predict the efficacy of selegiline monotherapy for motor symptoms in drug-naïve PD patients. Methods: We observed the efficacy of selegiline monotherapy in 28 drug-naïve PD patients and compared the improvement in motor function and the imaging findings. These patients received selegiline monotherapy, and the amount was increased to the optimal dose in clinical practice. Motor function was assessed using the Unified Parkinson's Rating Scale (UPDRS) at baseline and at the stable dose. Imaging was performed before treatment, and the striatal Specific Binding Ratio (SBR) of the 123I-Ioflupane SPECT and the Heart-to-Mediastinum (H/M) ratio of the 123I-MIBG myocardial scintigraphy were calculated. Both ratios were compared with improvements in scores for motor assessment using Pearson's correlation coefficient. Results: The mean UPDRS part III score significantly improved with at least 5.0 mg/day of selegiline. Further dose escalation did not improve the mean motor score. The percent improvement in the motor score from baseline showed a significant negative correlation with the SBR of average of the right and left striatum, but not with the H/M ratio. Multiple regression analysis using patient's background factors showed that percent improvement in the UPDRS part III score directly correlate with the SBR (p = 0.04), but not with the age (p = 0.72), disease duration (p = 0.31), baseline UPDRS part III (p = 0.77) and the drug dose (p = 0.26). Conclusion: PD patients with a lower accumulation of 123I-Ioflupane in the striatum can have greater improvement with selegiline monotherapy.

[Correlation between cognitive impairment and postural instability in patients with Parkinson's disease].

Correlation between frontal-executive function and motor functions, such as gait and postural control, has attracted attention in Parkinson's disease (PD). However, correlations between other cognitive functional domains and motor functions have not been examined. Thus, we examined the correlation between different domains of cognitive function and motor functions. Sixty-five PD patients were recruited for the present study. Cognitive functions were assessed by the 10 subtests of the Neurobehavioral Cognitive Status Examination (COGNISTAT). Motor functions were assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) as partIII for general motor function and sum of related items for tremor, rigidity, bradykinesia, and postural instability. Spearman's correlation coefficients between each cognitive and motor assessment were compared. Among the 10 subtests of the COGNISTAT, constructions showed significant correlation with UPDRS partIII (p<0.01), bradykinesia (p<0.01), and postural instability (p<0.001). The latter correlation was stronger than those between all motor assessments and both all patients backgrounds and other COGNISTAT subtests. In PD patients, postural instability correlates with not only frontal executive dysfunctions but also parietal dysfunctions, such as visuospatial and constructive impairments. The postural maintenance system is suggested to share common physiology with not only frontal-executive function but also parietal functions.

5-fluorouracil-induced leukoencephalopathy with acute stroke-like presentation fulfilling criteria for recombinant tissue plasminogen activator therapy.

A 61-year-old man underwent systemic chemotherapy with intravenous infusion of nedaplatin and 5-fluorouracil. On the day after the final drug administration, he suddenly experienced difficulty in speaking followed by left-sided weakness. His National Institutes of Health Stroke Scale score was 12. A computed tomographic scan of the brain performed 4 hours after symptom onset revealed no abnormalities. Because all eligibility criteria were fulfilled, he immediately underwent intravenous recombinant tissue plasminogen activator therapy. He recovered from neurologic complications on day 14. An initial magnetic resonance imaging scan of his brain revealed a hyperintense area in the bilateral white matter and corpus callosum, and these abnormalities had improved on the follow-up scan. We diagnosed him with 5-fluorouracil-induced leukoencephalopathy with acute stroke-like presentation. Our experience suggests that 5-fluorouracil-induced leukoencephalopathy potentially fulfills all eligibility criteria for recombinant tissue plasminogen activator therapy.

Cerebral microhemorrhage in Marchiafava-Bignami disease detected by susceptibility-weighted imaging.

Marchiafava-Bignami disease (MBD) is a rare alcohol-associated disorder. Clinical features include not only disturbed consciousness, dysarthria, tetraparesis, astasia-abasia, and symptoms of interhemispheric disconnection as initial symptoms but also cognitive deficits as clinical outcomes. The clinical significance of cerebral microhemorrhage (CMH) has been recognized in patients with cognitive deficits; however, the presence of CMH in patients with MBD has not been emphasized. The aim of the present study was to clarify the relationship between CMH and MBD. For this purpose, we report four patients with MBD, who showed asymmetrical hypointense areas in multiple cortico-subcortical regions on susceptibility-weighted imaging (SWI). All cases had a history of chronic alcohol abuse and symmetrical lesions in the entire corpus callosum. These patients' clinical symptoms included not only coma, dysarthria, and astasia-abasia as initial symptoms but also dementia as a clinical outcome. SWI showed asymmetrical hypointense areas in the multiple cortico-subcortical regions, indicating the presence of CMH. Compared with patients with normal cognitive function, demented patients showed higher severity of CMH. Our report would indicate that CMH is an important factor indicating the severity of dementia in patients with MBD.