Neuroinflammation following anti-parkinsonian drugs in early Parkinson's disease: a longitudinal PET study.

The progression of neuroinflammation after anti-parkinsonian therapy on the Parkinson's disease (PD) brain and in vivo evidence of the therapy purporting neuroprotection remain unclear. To elucidate this, we examined changes in microglial activation, nigrostriatal degeneration, and clinical symptoms longitudinally after dopamine replacement therapy in early, optimally-controlled PD patients with and without zonisamide treatment using positron emission tomography (PET). We enrolled sixteen PD patients (Hoehn and Yahr stage 1-2), and age-matched normal subjects. PD patients were randomly divided into two groups: one (zonisamide+) that did and one (zonisamide-) that did not undergo zonisamide therapy. Annual changes in neuroinflammation ([11C]DPA713 PET), dopamine transporter availability ([11C]CFT PET) and clinical severity were examined. Voxelwise differentiations in the binding of [11C]DPA713 (BPND) and [11C]CFT (SUVR) were compared with normal data and between the zonisamide+ and zonisamide- PD groups. The cerebral [11C]DPA713 BPND increased with time predominantly over the parieto-occipital region in PD patients. Comparison of the zonisamide+ group with the zonisamide- group showed lower levels in the cerebral [11C]DPA713 BPND in the zonisamide+ group. While the striatal [11C]CFT SUVR decreased longitudinally, the [11C]CFT SUVR in the nucleus accumbens showed a higher binding in the zonisamide+ group. A significant annual increase in attention score were found in the zonisamide+ group. The current results indicate neuroinflammation proceeds to the whole brain even after anti-parkinsonian therapy, but zonisamide coadministration might have the potential to ameliorate proinflammatory responses, exerting a neuroprotective effect in more damaged nigrostriatal regions with enhanced attention in PD.

In vivo Illustration of Altered Dopaminergic and GABAergic Systems in Early Parkinson's Disease.

Background: Changes in γ-aminobutyric acid (GABA) function are noted in patients with Parkinson's disease (PD) who have some non-motor impairments. However, dopamine-related GABA function and GABA-related cognitive changes are still unclear. Methods: Thirteen drug-naive early-stage PD patients underwent a series of PET scans with [11C]flumazenil(FMZ) and [11C]CFT. The [11C]FMZ binding potential (BPND) derived from a Logan plot analysis was compared between PD patients and age-matched controls. The [11C]CFT radioactivity relative to the cerebellar counterpart was estimated as a semiquantitative value [11C]CFT SUVR. Correlations between [11C]FMZ BPND and [11C]CFT SUVR in the same region of interest were also examined. Results: In patients in the PD group, [11C]CFT SUVR was significantly lower in the putamen. The levels of [11C]FMZ BPND in the cerebral cortex (frontal lobe dominancy) and the affected-side putamen were also reduced. In addition, [11C]CFT SUVR was negatively correlated with the [11C]FMZ BPND level in the affected-side putamen. In patients in the PD group, the total frontal assessment battery (FAB) score was positively correlated with the [11C]FMZ BPND in the frontal region. Conclusion: GABAergic dysfunction coexists with dopaminergic loss not only in the putamen but also over the extrastriatal region in patients with early PD and is related to frontal dysfunction. The negative correlation of [11C]CFT SUVR with [11C]FMZ BPND in the affected putamen suggests that a greater dopaminergic demise would decelerate GABA release (or an increase in tracer binding), resulting in persistent failure of the GABAergic system in PD patients.

[A case of colchicine myopathy in which the long-term use of colchicine hampered the recovery].

A 69-year-old woman was admitted to our hospital because of limb weakness. She was diagnosed to have chronic renal failure due to diabetes mellitus and had suffered from pericardial effusion at 67 years of age. She started taking colchicine 18 months before admission and thereafter gradually developed muscle weakness in her limbs and had become bedridden at the time of admission. The withdrawal of colchicine improved her limb weakness, and therefore we diagnosed her to have colchicine myopathy. Her muscle strength did not completely recover even after six months from cessation of colchicine. It was suggested that renal failure and muscle disuse had prevented the full recovery of her muscles in addition to the long-term use of colchicine. Typical colchicine myopathy improves rapidly, but the long-term use of colchicine is considered to cause muscle weakness. Although the CK level was elevated, the elevated CK and myopathy had been overlooked because the CK baseline was low due to the patient's small amount of muscle mass. Moreover, the estimated GFR was recorded to be higher than her actual renal function due to her small amount of muscle mass, therefore the risk of colchicine myopathy in this case remained unrecognized.

[A case of human adjuvant disease with clinical features of Guillain-Barré syndrome].

A 69-year-old female developed subacute diplopia, right peripheral facial nerve palsy, bilateral upper and lower extremities dysesthesia and weakness 50 years after silicone injection for breast augmentation. Motor conduction study revealed prolonged distal latency and reduced amplitude in the median, ulnar, and peroneal nerves. Sensory conduction velocities were reduced in the median and ulnar nerves, and sensory potential in the sural nerve could not be recorded. While intravenous immunoglobulin therapy was ineffective, explantation of silicone breast implants improved her neurological symptoms. Histopathological study of axillary lymph node revealed foreign body granulomas and macrophages phagocyting silicone. The patient was diagnosed with human adjuvant disease presenting clinical features of Guillain-Barré syndrome. Human adjuvant disease should be considered in the patients with implants like silicone and neurological symptoms.

[Ischemic changes and blood coagulation abnormalities as complications of pneumococcal meningitis].

One explanation for cerebral infarctions that occur as a complication of pneumococcal meningitis is blood coagulation abnormalities. We investigated the clinical features, laboratory test results, magnetic resonance imaging (MRI) findings, and pathological features of 10 patients with pneumococcal meningitis between 2006 and 2013 to examine the abnormal findings that may be associated with prognosis. Five patients (50%) that had Glasgow Outcome Scale scores between 1 and 4 were classified as the poor outcome group. In this group, the MRI revealed a high signal intensity on the diffusion-weighted image (DWI), and there was an abnormal signal along the cerebral cortex and Virchow-Robin spaces, which were characterized pathologically by ischemic changes. The plasma thrombin-antithrombin complex (TAT) levels showed greater differences between the poor and good prognosis groups than platlet and D-dimer levels; this suggested that high plasma TAT levels indicate a poor prognosis.