Brain regions associated with cognitive impairment in patients with Parkinson disease: quantitative analysis of cerebral blood flow using 123I iodoamphetamine SPECT.

PURPOSE: Cognitive impairment is a representative neuropsychiatric presentation that accompanies Parkinson disease (PD). The purpose of this study was to localize the cerebral regions associated with cognitive impairment in patients with PD using quantitative SPECT. PATIENTS AND METHODS: Thirty-two patients with PD (mean [SD] age, 75 [8] years; 25 women; Hoehn-Yahr scores from 2 to 5) underwent quantitative brain SPECT using 123I iodoamphetamine. Parametric images of regional cerebral blood flow (rCBF) were spatially normalized to the standard brain atlas. First, voxel-by-voxel comparison between patients with PD with versus without cognitive impairment was performed to visualize overall trend of regional differences. Next, the individual quantitative rCBF values were extracted in representative cortical regions using a standard region-of-interest template to compare the quantitative rCBF values. RESULTS: Patients with cognitive impairment showed trends of lower rCBF in the left frontal and temporal cortices as well as in the bilateral medial frontal and anterior cingulate cortices in the voxel-by-voxel analyses. Region-of-interest-based analysis demonstrated significantly lower rCBF in the bilateral anterior cingulate cortices (right, 25.8 [5.5] vs 28.9 [5.7] mL per 100 g/min, P < 0.05; left, 25.8 [5.8] vs 29.1 [5.7] mL per 100 g/min, P < 0.05) associated with cognitive impairment. CONCLUSIONS: Patients with cognitive impairment showed lower rCBF in the left frontal and temporal cortices as well as in the bilateral medial frontal and anterior cingulate cortices. The results suggested dysexecutive function as an underlining mechanism of cognitive impairment in patients with PD.

Writing errors in ALS related to loss of neuronal integrity in the anterior cingulate gyrus.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by loss of motor neuron and various cognitive deficits including writing errors. (11)C-flumazenil (FMZ), the positron emission tomography (PET) GABA(A) receptor ligand, is a marker of cortical dysfunction. The objective of this study was to investigate the relationship between cognitive deficits and loss of neuronal integrity in ALS patients using (11)C-FMZ PET. Ten patients with ALS underwent both neuropsychological tests and (11)C-FMZ-PET. The binding potential (BP) of FMZ was calculated from (11)C-FMZ PET images. There were no significant correlations between the BP and most test scores except for the writing error index (WEI), which was measured by the modified Western Aphasia Battery - VB (WAB-IVB) test. The severity of writing error was associated with loss of neuronal integrity in the bilateral anterior cingulate gyrus with mild right predominance (n=9; x=4 mm, y=36 mm, z=4 mm, Z=5.1). The results showed that writing errors in our patients with ALS were related to dysfunction in the anterior cingulate gyrus.

Adult Leigh disease without failure to thrive.

INTRODUCTION: Most Leigh disease (LD) patients die before reaching adulthood, but there are reports of "adult LD." The clinical features of adult LD were quite different from those in infant or childhood cases. Here, we describe a normally developed patient with adult LD, who presented with spastic paraplegia that was followed several years later by acute encephalopathy. We also conducted a systemic literature search on adult LD and integrated its various manifestations to arrive at a diagnostic procedure for adult LD. CASE REPORT: A 26-year-old woman presented with acute encephalopathy after spastic paraplegia. On her first admission, she exhibited bilateral basal ganglia lesion on magnetic resonance images and normal serum lactate levels. On second admission, she had acute encephalopathy with lactic acidosis and bilateral basal ganglia and brainstem lesions. A muscle biopsy revealed cytochrome c oxidase deficiency, and a diagnosis of adult LD was made. Despite treatment in the intensive care unit, she died 9 days after admission. CONCLUSIONS: A review of the literature describing adult LD revealed that developmental delay, COX deficiency, serum lactate elevation, and basal ganglia lesions occurred less frequently than they did in children with LD. Cranial nerve disturbance, pyramidal signs, and cerebellar dysfunction were the primary symptoms in adult LD. Thus, the many differences between childhood and adult LD may be helpful for diagnosing adult LD.

[A case of primary diffuse leptomeningeal gliomatosis, clinically indistinguishable from metastatic meningeal carcinomatosis].

A 65-year-old woman presented with progressive gait disturbance. She complained of appetite loss for 3 months. Her gait gradually became unsteady, and she was admitted to our hospital. On admission, slow mentation, bathyhypesthesia in left upper and both lower extremites, positive Romberg sign and wide-based gait were observed. Gd-enhanced MRI revealed mass lesions in the left temporal fossa and the cervical spinal canal with focal meningeal enhancement. Besides lesions in the central nervous system (CNS), systematic examination detected no additional malignancy. Repeated cytology of the cerebrospinal fluid was negative. After admission, her consciousness became reduced gradually. At 2 months after admission, she died of central respiratory failure. On autopsy, diffuse extension of the tumor cells was observed on the surface of CNS, and the mass lesions observed by MRI were extra-parenchymal On microscopic examination, the mass was consisted of GFAP positive malignant cells, and included perivascular pseudorosette, pseudopalisading necrosis and many mitotic cells. The diagnosis of the case was made as primary diffuse leptomeningeal gliomatosis (PDLG). PDLG is a rare disorder that is difficult to diagnose by CSF cytology. The progress of PDLG is rapid, and appropriate treatment is rarely taken. However, the combination of temozolomide and the radiotherapy performed for a glioblastoma has been reported as a possible treatment for PDLG. We emphasize that, in possible cases of PDLG, a biopsy should be performed in the early stages, especially in cases showing features similar to those of metastatic meningeal carcinomatosis and have no malignant tumors by whole body examination.

FDG-PET SUV can distinguish between spinal sarcoidosis and myelopathy with canal stenosis.

Spinal cord sarcoidosis is a rare manifestation of sarcoidosis. Magnetic resonance imaging (MRI) of spinal cord sarcoidosis sometimes resembles that of the non-inflammatory spinal cord lesion. (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) is an effective method to detect both systemic and central nervous system lesions in sarcoidosis. This study compared the standard uptake value (SUV) of FDG-PET between spinal cord sarcoidosis and non-inflammatory spinal cord lesions. We retrospectively reviewed the records of patients who underwent both spinal MRI and FDG-PET scans. We used SUV to evaluate the FDG-PET uptake of the lesion. The region of interest was the center of high-intensity areas on T2-weighted MR images. We included three patients with spinal cord sarcoidosis, five with myelomalacia caused by cervical spondylosis or ossification of the posterior longitudinal ligament, one with spinal cord edema associated with cervical spondylosis, and one with spinal cord edema associated with dural arteriovenous fistula. The spinal cord sarcoidosis group had a significantly higher SUV (mean 4.38, range 3.30-4.93) than patients with the other diseases (mean 1.87, range 1.42-2.74). The SUV of FDG-PET thus may be able to distinguish spinal cord sarcoidosis from other non-inflammatory lesions. FDG-PET can play an important role in the diagnosis of spinal cord sarcoidosis because the gadolinium enhancement in MRI is sometimes seen in spondylotic myelopathy or vascular malformation. FDG-PET is informative for the accurate diagnosis of spinal cord sarcoidosis and may enable clinicians to start treatment at an earlier stage.

Idiopathic hypoglossal nerve laceration detected by high-resolution three-dimensional constructive interference in steady state magnetic resonance imaging.

A 55-year-old man presented with acute onset dysarthria caused by left hypoglossal palsy. He had neither surgery nor injury prior to the onset of his symptoms. We detected no abnormalities with conventional magnetic resonance imaging (MRI) except for a slight gadolinium enhancement of the left hypoglossal nerve. Three-dimensional constructive interference in steady state MRI (CISS MRI) showed curling and thickening of the left hypoglossal nerve and fluid accumulation in the hypoglossal nerve canal. A systemic survey found no malignancies. After 8 months, sustained left hypoglossal palsy and no change in the MRI led to the diagnosis of idiopathic hypoglossal nerve laceration with evulsion. In such patients, the cause of the defect is not always apparent and 3-dimensional CISS MRI may resolve this issue.

Writing errors as a result of frontal dysfunction in Japanese patients with amyotrophic lateral sclerosis.

Loss of communication is a critical problem for advanced amyotrophic lateral sclerosis (ALS) patients. This loss of communication is mainly caused by severe dysarthria and disability of the dominant hand. However, reports show that about 50% of ALS patients have mild cognitive dysfunction, and there are a considerable number of case reports on Japanese ALS patients with agraphia. To clarify writing disabilities in non-demented ALS patients, eighteen non-demented ALS patients and 16 controls without neurological disorders were examined for frontal cognitive function and writing ability. To assess writing errors statistically, we scored them on their composition ability with the original writing error index (WEI). The ALS and control groups did not differ significantly with regard to age, years of education, or general cognitive level. Two patients could not write a letter because of disability of the dominant hand. The WEI and results of picture arrangement tests indicated significant impairment in the ALS patients. Auditory comprehension (Western Aphasia Battery; WAB IIC) and kanji dictation also showed mild impairment. Patients' writing errors consisted of both syntactic and letter-writing mistakes. Omission, substitution, displacement, and inappropriate placement of the phonic marks of kana were observed; these features have often been reported in Japanese patients with agraphia resulted from a frontal lobe lesion. The most frequent type of error was an omission of kana, the next most common was a missing subject. Writing errors might be a specific deficit for some non-demented ALS patients.

Clinical characterization and successful treatment of 6 patients with Churg-Strauss syndrome-associated neuropathy.

OBJECTIVE: To confirm the reported findings and clarify unknown clinical features of Churg-Strauss syndrome (CSS)-associated neuropathy and design appropriate treatment. PATIENTS AND METHODS: We assessed the clinical features of 6 patients with CSS-associated neuropathy. RESULTS: Mononeuritis multiplex was present in 4 cases and polyneuropathy in the remaining cases. Both groups progressed to sensori-motor polyneuropathy in an acute or subacute course. All cases showed bronchial asthma and eosinophilia. Two cases with serum antineutrophil cytoplasmic antibodies to myeloperoxidase (MPO-ANCA) had an acute clinical course and severe symptoms. Nerve conduction studies (NCS) of these 2 cases revealed conduction blocks at the initial stage, although NCS finally indicated sensori-motor axonopathy at the involved extremities. For treatment, high-dose corticosteroid therapy for 4 cases, and cyclophosphamide combined with corticosteroids for 1 case, were effective. For the remaining case, intravenous immunoglobulin (IVIg) at the chronic phase resulted in a slow improvement of neuropathy in the symptomatic aspect. There was no relapse of neuropathy with low-dose corticosteroid treatment for 14-24 months after the initial treatment, except 1 case. There was also no relapse in the other case that was treated with moderate-dose steroids. CONCLUSION: Our study showed that CSS-associated neuropathy is a treatable disorder and that the first choice therapy is high-dose corticosteroid. In cases where corticosteroids are ineffective or for severe cases, immunosuppressive therapy (cyclophosphamide) with steroids should be considered, and IVIg might be a treatment option.

Cystatin C in cerebrospinal fluid as a biomarker of ALS.

Amyotrophic lateral sclerosis (ALS) is diagnosed on the basis of progressive symptoms in both the upper and lower motor neurons. Because there are no specific biomarkers for ALS, it is difficult to diagnose this disease in its early stages. Cerebrospinal fluid (CSF) samples were obtained from 14 patients in the early stages of ALS, from 13 with polyneuropathy, and from 16 with other neurological disorders. The concentration of cystatin C in the CSF was measured using a sandwich enzyme-linked immunosorbent assay (ELISA) kit. The concentration of cystatin C in the CSF was significantly lower in ALS patients than in the control subjects who were patients with polyneuropathy or other neurological diseases (patients with ALS, polyneuropathy, and other diseases exhibited 5.5 +/- 0.3, 6.7 +/- 0.4, and 6.9 +/- 0.3 mg/L cystatin C, respectively; ALS patients vs. control subjects: p = 0.014 and ALS patients vs. polyneuropathy patients: p = 0.024). Cystatin C may be a useful biomarker of ALS and can be used to distinguish between ALS and polyneuropathy.