[(123)I]-Ioflupane SPECT in combination with MIBG myocardial scintigraphy in Parkinson's disease: a case series study.

Metaiodobenzylguanidine (MIBG) myocardial scintigraphy is widely accepted as a beneficial tool for differentiating Parkinson's disease (PD) from other Parkinson-related disorders (PRD). In Japan, dopamine transporter (DAT) imaging, which can evaluate presynaptic degeneration of dopamine neurons, has been applied in clinics since 2014. The present study investigated the utility of [(123)I]-Ioflupane single photon emission computed tomography (SPECT) combined with MIBG myocardial scintigraphy for the diagnosis of PD. We performed [(123)I]-Ioflupane SPECT and MIBG myocardial scintigraphy in 63 PD patients, 8 PRD patients and 1 essential tremor patient, and obtained the specific binding ratio (SBR [cut-off: 4.5]) and the heart-to-mediastinum ratio (H/M [cut-off: 2.2]). In 70% of the PD patients, both parameters were significantly reduced. In 22% of the PD patients, the SBR was smaller than 4.5 with normal H/M, and H/M was less than 2.2 with normal SBR in 5% of all subjects. Either the SBR or H/M was significantly reduced in 97% of the study population. The SBR showed low disease specificity to PD (11%), and the SBR and H/M negatively correlated with disease duration. These findings indicate that [(123)I]-Ioflupane SPECT combined with MIBG myocardial scintigraphy can improve the detection rate of PD. However, careful interpretation of these results is required because [(123)I]-Ioflupane SPECT poorly differentiates PD from PRD. Progression of PD may reflect the gradual reduction of isotope accumulation, hence, both [(123)I]-Ioflupane SPECT and MIBG myocardial scintigraphy should be tested repeatedly even in clinically suspected PD cases showing negative results.

[A case of orbital apex syndrome due to aspergillus infection that avoided loss of visual acuity by optic canal decompression].

A 71-year-old woman was admitted to our hospital complaining of left orbital pain, headache, diplopia and left-sided ptosis, which she had suffered for two months. On examination, the patient had loss of visual acuity, left-sided ptosis, lateral gaze disturbance, and was diagnosed as having left orbital apex syndrome. An abnormal signal to the left orbital cone was detected on MRI. Serum ß-D-glucan was increased, and serum Aspergillus antigen and antibody were both positive. Although antifungal drugs (voriconazole and liposomal amphotericin B) were administered, the symptoms deteriorated. The patient then underwent optic nerve decompression surgery and was treated with intravenous methylprednisolone, which gradually improved the patient's symptoms, Aspergillus hyphae were confirmed by pathological examination. To obtain good prognosis for patients with orbital apex syndrome associated with Aspergillus infection, optic nerve decompression surgery should be considered.

Characteristic features and progression of abnormalities on MRI for CARASIL.

OBJECTIVES: The objective of this study was to clarify the characteristic brain MRI findings for genetically diagnosed CARASIL (cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy). METHODS: Seven patients with CARASIL carrying HTRA1 mutations (representing 6 Japanese families) were included in this study. Eighteen brain MRIs were reviewed and evaluated with a new rating scale based on scoring for abnormal hyperintense lesions and atrophy. RESULTS: At the last follow-up MRI, all patients had hyperintense lesions on T2-weighted images of the frontal white matter, anterior temporal lobe, external capsules, and thalami. Patients with longer time from the onset of cognitive impairment had higher MRI severity score. The atrophy advanced, followed by white matter lesion progression. During the early stage, hyperintense lesions were observed in the frontal white matter, external capsule, and pons. During the late stage, the arc-shaped hyperintense lesion from the pons to the middle cerebellar peduncles, which we designated the "arc sign," became evident. The arc sign was a characteristic finding for CARASIL in the advanced stage. CONCLUSIONS: These characteristic MRI findings for CARASIL are useful for selecting patients for genetic testing. The rating scale correlates well with disease duration and might be useful for assessing disease progression.

Involvement of spinal motor neurons in parkin-positive autosomal recessive juvenile parkinsonism.

We intensively examined the spinal cord of an autosomal recessive juvenile parkinsonism (ARJP) female patient with a homozygous exon 3 deletion in the parkin gene, anticipating a possible involvement of anterior horn neurons. Although the clinical features of the patient were consistent with parkinsonism as a result of parkin mutation, her tendon reflex was abolished in the lower limbs. This feature was in contrast with hyperreflexia, usually found in previous reports of ARJP. Histologically, on the level of the cervical, thoracic, and sacral spinal cord, anterior horn neurons were well preserved and normal. However, the lumbar spinal cord exhibited many swellings of proximal axons (spheroids) and degenerative changes in the somata of the large anterior horn neurons such as central chromatolysis, cystatin C-negative small eosinophilic inclusions, and eosinophilic Lewy body-like inclusions. Ultrastructurally, accumulations of neurofilaments and abnormal structures, such as inclusion bodies similar to skein-like inclusions and disorganized rough endoplasmic reticulum, were observed in the somata and neuronal processes. Lewy body-like inclusions in this study were positively immunostained for both alpha-synuclein and ubiquitin that closely resemble Lewy bodies, but are different from Lewy body-like inclusions negatively immunostained for alpha-synuclein in amyotrophic lateral sclerosis. These findings suggest that eosinophilic inclusions that closely resemble Lewy bodies may be formed in the spinal motor neurons of ARJP patients with parkin mutations and the motor neurons of these patients may be vulnerable to neurodegeneration.

[Case of Isaacs' syndrome associated with Hashimoto disease].

We report a case of Isaacs' syndrome associated with Hashimoto disease. A 26-year-old woman, who had a past history of Hashimoto disease, complained of involuntary movements and muscle cramp in lower extremities. On examination, myokymia was seen in lower extremities. Myokymia was observed even during sleep, and worsened by exercise or bathing. The antibody against voltage-gated potassium channel (VGKC) was positive. Myokymic discharges were recorded with needle EMG in lower extremities. The patient was diagnosed as having Isaacs' syndrome. Isaacs' syndrome tends to be associated with some other autoimmune diseases. We discussed the correlation between Isaacs' syndrome and autoimmune disease. About 23% of Isaacs' syndrome cases are associated with some other autoimmune diseases and myasthenia gravis was most common. This is the first case report of Isaacs' syndrome associated with Hashimoto disease in Japan.

Parkin-positive autosomal recessive juvenile Parkinsonism with alpha-synuclein-positive inclusions.

OBJECTIVE: To report an autopsy case of an autosomal recessive juvenile parkinsonism patient with a homozygous exon 3 deletion in the parkin gene and alpha-synuclein-positive inclusions. METHODS: The representative areas of the brain were embedded in paraffin, stained with hematoxylin-eosin, Klüver-Barrera, and Gallyas-Braak stainings. Immunohistochemically, some of the specimens were used for immunostaining with the antibodies to alpha-synuclein, ubiquitin, and phosphorylated tau (AT8). Immunoreaction was visualized by the streptavidin-biotin-peroxidase complex method. RESULTS: Histologically, the lesions of the brain were limited to the dopaminergic neuron system such as the substantia nigra (SN) and locus ceruleus. Melanin-containing neurons in the pars compacta of the SN were moderately to severely depleted, accompanied by gliosis. In the locus ceruleus, neurons were mildly decreased and extraneuronal melanin pigments were seen. Lewy bodies were not observed in the neuropils of the pars compacta of the SN or locus ceruleus. However, basophilic inclusion bodies were only occasionally observed in the neuropils of the pedunculopontine nucleus in the mesencephalic reticular formation. Immunohistochemistry with antibodies to alpha-synuclein and ubiquitin showed alpha-synuclein- and ubiquitin-positive inclusions in the neuropils of the pedunculopontine nucleus, which had a doughnut or round shape. CONCLUSIONS: A variety of parkin gene abnormalities may produce pathologic differences in the degree and distribution of neuronal degeneration, including the absence or presence of Lewy bodies. A relationship between parkin-induced parkinsonism and idiopathic Parkinson disease (PD) may exist.