Clinical characteristics of autoimmune GFAP astrocytopathy.

The clinical features of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy remain to be elucidated. We describe here the clinical features of 14 patients with GFAP astrocytopathy confirmed by detection of GFAP-IgG in cerebrospinal fluid (CSF). The novel findings of this study are as follows. First, over half of the patients presented with movement disorders (tremor, myoclonus, and ataxia), autonomic dysfunction (mainly urinary dysfunction), and hyponatremia. Second, most patients showed transient elevation of adenosine deaminase activity levels in CSF. Finally, some patients showed bilateral hyperintensities in the posterior part of the thalamus on brain magnetic resonance imaging.

Inorganic phosphorus (Pi) in CSF is a biomarker for SLC20A2-associated idiopathic basal ganglia calcification (IBGC1).

INTRODUCTION: Idiopathic basal ganglia calcification (IBGC), also called Fahr's disease or recently primary familial brain calcification (PFBC), is characterized by abnormal deposits of minerals including calcium mainly and phosphate in the brain. Mutations in SLC20A2 (IBGC1 (merged with former IBGC2 and IBGC3)), which encodes PiT-2, a phosphate transporter, is the major cause of IBGC. Recently, Slc20a2-KO mice have been showed to have elevated levels of inorganic phosphorus (Pi) in cerebrospinal fluid (CSF); however, CSF Pi levels in patients with IBGC have not been fully examined. METHODS: We investigated the cases of 29 patients with IBGC including six patients with SLC20A2 mutation and three patients with PDGFB mutation, and 13 controls. The levels of sodium (Na), potassium (K), chloride (Cl), calcium (Ca), and Pi in sera and CSF were determined by potentiometry and colorimetry. Moreover, clinical manifestations were investigated in the IBGC patients with high Pi levels in CSF. RESULTS: The study revealed that the average level of Pi in the CSF of the total group of patients with IBGC is significantly higher than that of the control group, and the levels of Pi in CSF of the IBGC patients with SLC20A2 mutations are significantly higher than those of the IBGC patients with PDGFB mutations, the other IBGC patients and controls. CONCLUSION: Results of this study suggest that the levels of CSF Pi will be a good biomarker for IBGC1.

Decreased regional cerebral blood flow in the bilateral thalami and medulla oblongata determined by an easy Z-score (eZIS) analysis of (99m)Tc-ECD-SPECT images in a case of MM2-thalamic-type sporadic Creutzfeldt-Jakob disease.

We report a case of autopsy-verified MM2-thalamic-type sporadic Creutzfeldt-Jakob disease (sCJD) in a 46-year-old patient with a 16-month history of abnormal behavior, progressive dementia, insomnia, and speech disturbances without family history. Neurological examination revealed progressive dementia, frontal signs, insomnia, speech disturbance, gait disturbance and bilaterally exaggerated tendon reflexes. Both brain MRI and cerebrospinal fluid examinations, including 14-3-3 protein, yielded normal results. An easy Z-score (eZIS) analysis for (99m)Tc-ethyl cysteinate dimer-single photon emission computed tomography ((99m)Tc-ECD-SPECT) revealed decreased regional cerebral blood flow in the bilateral thalami and medulla oblongata. PRNP gene analysis revealed methionine homozygosity at codon 129 without mutation. Neuropathological examinations revealed severe neuronal loss, gliosis, and hypertrophic astrocytosis in the medial thalamus and inferior olivary nucleus. A slight depletion of Purkinje cells was observed. PrP immunostaining showed no obvious PrP deposits in the basal ganglia, thalamus, cerebellum, or brainstem; however, mild synaptic-type PrP deposits with some smaller plaque-like structures were only partially observed in the localized region of the frontal lobe with the spongiform change. Western blot analyses of protease-resistant PrP showed a type 2 pattern. In conclusion, eZIS analysis of (99m)Tc-ECD-SPECT images is useful for detecting both thalamic and medullary lesions. This is the first case of medullary lesions detected in a live patient with MM2-thalamic-type sCJD using SPECT.

Decreased bioelements content in the hair of patients with Fahr's disease (idiopathic bilateral calcification in the brain).

The remarkable calcification of the basal ganglia and cerebellum has been traditionally called Fahr's disease, but this nomenclature is criticized for including heterogeneous diseases. To determine the pattern of some biological metals in the hair of patients with Fahr's disease, we investigated the levels of 24 bioelements in the hair of 28 patients (17 males and 11 females) with Fahr's disease and compared them with those of three age-, sex-, and living region-matched controls (84 controls in total). Interestingly, we found decreases in the levels of several bioelements [calcium (Ca), copper (Cu), iron (Fe), mercury (Hg), iodine (I), nickel (Ni), phosphate (P), lead (Pb), and selenium (Se)] in the hair of patients. This is in contrast to our previous finding of increases of Cu, Fe, zinc (Zn), and magnesium (Mg) in the cerebrospinal fluid (CSF) of patients. The decreased level of Cu in the hair was the most prominent and pathognomonic, while the increased level of Cu in the CSF had been found to be the most significant in patients. More significant correlations between two bioelements in the hair were recognized in patients than controls. Although Fahr's disease has been considered to be a heterogenous entity, the significant tendencies of several bioelements in the hair of patients in this study suggest metabolic disorders of bioelements, especially biometals, on the background. Some transporters, especially P transporter such as PiT2, of bioelements will be involved in the different distribution of bioelements in the body of patients.