Hypoperfusion in Supramarginal and Orbital Gyrus, Position Discrimination Test, and Microsaccades as a Predictor of Pisa Syndrome in Parkinson's Disease.

Patients with Parkinson's disease (PD) experience significantly reduced quality of life when PD is complicated with Pisa syndrome (PS). PS is a postural abnormality associated with a lateral bending of the trunk, causing the patient to lean to one side. Microsaccades during fixation are transmitted to the visual cortex, and this gaze movement may be impaired in PD. We aimed to detect presymptomatic signs of PS. We enrolled 50 patients with PD without dementia and investigated the visual systems in patients with concurrent PD and PS based on a Romberg ratio of<1.0. Gaze analysis, pupil diameter, stabilization tests, neuropsychological tests, and cerebral perfusion scintigraphy were reviewed and statistically analyzed. Two years later, we divided the patients into three groups as follows: PISA++ (patients who had PS at enrollment), PISA-+ (patients without PS that developed PS during the 2-year period), and PISA-- (patients without PS that did not develop PS during the 2-year period). The PISA-+ group exhibited a significantly higher daily levodopa dose and longer fixations, as well as lower position discrimination, Wechsler Adult Intelligence Scale-Third Edition blocking, and blood flow in the left supramarginal and orbital gyri than that in the PISA-- group. The PISA++ group showed a significantly longer fixation time and lower Mini-Mental State Examination score, Romberg ratio of area, amplitude, velocity of microsaccades, and blood flow in the left precuneus and cuneus than that in the PISA-+ group. Before the onset of PS, hypoperfusion occurred in the correlative visual cortex and the position discrimination test. Patients with PS have reduced saccades and slow microsaccades.

Tau aggregation and seeding analyses of two novel MAPT variants found in patients with motor neuron disease and progressive parkinsonism.

Variants in the microtubule-associated protein tau (MAPT) gene cause the genetic tauopathies, a subgroup of frontotemporal dementia (FTD) disorders. Through genetic screening of 165 cases possibly associated with tauopathies, including 88 Alzheimer's disease, 26 behavioral variant FTD, eight primary progressive aphasia, nine FTD with motor neuron disease, 21 progressive supranuclear palsy, and 13 corticobasal syndrome, we identified two novel MAPT variants: a heterozygous missense variant, p.P160S, in a patient with FTD with motor neuron disease and a heterozygous insertional variant, p.K298_H299insQ, in three patients with familial progressive supranuclear palsy. The corresponding recombinant tau proteins showed reduced microtubule assembly and increased aggregation by thioflavin S assay. Exon trapping analysis showed that p.K298_H299insQ resulted in the overproduction of 4-repeat tau. In a cell-based model, p.K298_H299insQ had both a higher aggregation ability and seeding activity compared with wild-type tau. These findings indicate that both p.P160S and p.K298_H299insQ may relate to neurodegeneration.

Marked Reduction in the Striatal Dopamine Transporter Uptake During the Early Stage of Motor Symptoms in Patients with the MAPT N279K Mutation.

We herein report two patients harboring the mutation N279K in microtubule-associated protein tau (MAPT), who showed parkinsonism with a disease duration within three years from the onset, evaluated by dopamine transporter (DAT) [123I]N-ω-fluoroprophyl-2ß-carbomethoxy-3ß-(4-iodophenyl) tropane single-photon emission computed tomography. We performed a quantification analysis, comparing five age- and severity-matched PD patients and six normal controls. The patients with the N279K mutation showed a more marked reduction in their DAT densities, especially in the caudate nucleus and anterior putamen, than the others. An early marked reduction in the DAT densities in the caudate nucleus and anterior putamen may be an early biomarker of patients with MAPT mutations.

Galantamine Response Associates with Agitation and the Prefrontal Cortex in Patients with Alzheimer's Disease.

Behavioral and psychological symptoms of dementia (BPSD) occur in up to 80% of AD patients and represent one of the largest factors contributing to caregiver burden. To analyze the effect of galantamine on BPSD and caregiver burden, we treated a total of 50 patients with mild AD for 12 weeks and evaluated them using the Neuropsychiatric Inventory (NPI) and Japanese version of the Zarit Caregiver Burden Interview (ZBI). We also performed regional cerebral blood flow single photon emission computed tomography (rCBF SPECT) at baseline using three-dimensional sterotatic surface projections. Total NPI and ZBI scores did not significantly change after 12-week galantamine treatment. To identify the characteristics of patients who showed improvement after galantamine treatment, we divided patients into two groups, those with and those without sub-items on the NPI. Patients with aggression showed improvement in ZBI scores (p < 0.05). A comparison of rCBF SPECT between these two groups indicated that patients with aggression exhibited increased rCBF in the right prefrontal cortex compared with those without aggression. In a patient with aggression, 20-month treatment with galantamine inhibited increases in the rCBF area in the right prefrontal lobe. These results suggest that galantamine response may be related to aggression and dysfunction of the prefrontal cortex.

Fibromyalgia syndrome and cognitive dysfunction in elderly: a case series.

AIM: Fibromyalgia syndrome (FMS) is an extremely rare complication of neurocognitive disorders (NCDs). We experienced seven such cases, and we discuss their clinical manifestation and pathomechanisms. METHODS: Seven patients with FMS as a complication of NCD were enrolled. We used the patients' medical records to identify clinical manifestations and obtain experimental data, such as pain questionnaire scores, cognitive tests, genetics and radiological imaging of the brain. RESULTS: The seven patients were clinically diagnosed with frontotemporal NCD (n = 3) or Alzheimer's disease (n = 4). No patient presented with any organic disorder that would explain their chronic pain. Through their courses, they experienced refractory widespread pain continuously despite analgesics. Brain magnetic resonance imaging revealed moderate or severe atrophic changes in the temporal lobes and hippocampus. Three-dimensional stereotactic surface projection (3D-SSP) analysis of brain single photon emission computed tomography (SPECT), indicated severe hypoperfusion on the right side of the medial temporal lobe, both sides of the anterior corpus callosum, anterior cingulate gyrus, and primary sensory area. Genetic analysis uncovered no pathogenic mutations. CONCLUSIONS: Neurodegenerative disorders are rarely complicated by FMS, which is associated with relatively severe pain. Central sensitization may be a possible risk factor of widespread pain in elderly patients with NCD.