Dementia in Parkinson's disease: diffusion tensor imaging.

OBJECTIVE: Dementia occurs frequently in patients with Parkinson's disease (PD). However, the nature of the dementing process remains controversial. We evaluated various cognitive functions in patients with PD, compared fractional anisotropy (FA) values between PD patients with and without dementia. METHODS: Thirty-seven consecutive patients with Hoehn-Yahr stage III or IV PD participated in this study. Patients were divided into two groups: (i) PD with dementia group (PDD) and (ii) PD without dementia group (PDND). There were 11 PDD and 26 PDND cases. Ten controls were also studied. RESULTS: The PDD group showed significant FA reduction in the bilateral posterior cingulate bundles compared with PDND. FA values in the left posterior cingulate bundle showed significant correlations with many cognitive parameters. INTERPRETATION: Our results showed that the posterior cingulate areas play some important roles in the dementing process in PDD. However, as the pathological processes responsible for dementia in PD patients may be multifaceted, further studies are necessary.

Wisconsin Card Sorting Test in Parkinson's disease: diffusion tensor imaging.

INTRODUCTION: It is generally assumed that executive dysfunctions in Parkinson's disease (PD) are caused by degeneration of the basal ganglia or frontal cortex or both. However, there have been few studies investigating the relationship between executive dysfunctions and cerebral pathological change. The objective of this study was to evaluate various cognitive functions in non-demented patients with PD, and to compare the fractional anisotropy (FA) values of PD patients with and without executive dysfunction. MATERIALS AND METHODS: Twenty-one consecutive non-demented patients with PD were enrolled in this study. Patients were divided into two groups on the basis of their Wisconsin Card Sorting Test score. RESULTS: There was significant FA reduction in the left parietal white matter in the group in which the number of categories achieved was 2. CONCLUSION: Accumulating evidence suggests that conventional 'frontal' tasks correlate with both frontal lobe and parietal lobe function, and we suggest that pathological changes in the left parietal lobe may cause, in part, disturbances in executive tasks in PD.

Regional cerebral blood flow in Parkinson disease with nonpsychotic visual hallucinations.

BACKGROUND: Patients with Parkinson disease (PD) often experience visual hallucinations (VH) with retained insight (nonpsychotic) but the precise mechanism remains unclear. OBJECTIVE: To clarify which neural substrates participate in nonpsychotic VH in PD, the authors evaluated regional cerebral blood flow (rCBF) changes in patients with PD and VH. METHODS: The authors compared 24 patients with PD who had nonpsychotic VH (hallucinators) and 41 patients with PD who had never experienced VH (non-hallucinators) using SPECT images with N-isopropyl-p-[(123)I]iodoamphetamine. There were no significant differences in age, sex, duration of disease, doses of PD medications, Hoehn and Yahr scale, or Mini-Mental State Examination (MMSE) scores between the two groups. The rCBF data were analyzed using statistical parametric mapping (SPM). RESULTS: The rCBF in the right fusiform gyrus was lower in the hallucinators than in the non-hallucinators (corrected p < 0.05 at cluster levels). The hallucinators revealed higher rCBF in the right superior and middle temporal gyri than the non-hallucinators (uncorrected p < 0.001). These significant differences were demonstrated after MMSE scores and duration of disease, which are the relevant factors associated with VH, were covariated out. CONCLUSIONS: Nonpsychotic visual hallucinations in Parkinson disease (PD) may be associated with hypoperfusion in the right fusiform gyrus and hyperperfusion in the right superior and middle temporal gyri. These temporal regions are important for visual object recognition and these regional cerebral blood flow changes are associated with inappropriate visual processing and are responsible for nonpsychotic visual hallucinations in PD.

Three-dimensional stereotactic surface projection study of orthostatic hypotension and brain perfusion image in Parkinson's disease.

OBJECTIVE: To compare brain perfusion image using three-dimensional stereotactic surface projection (3D-SSP) analysis of N-isopropyl-p-123I iodoamphetamine (123I-IMP) single photon emission computed tomography (SPECT) between patients with Parkinson's disease with orthostatic hypotension and those without orthostatic hypotension. MATERIALS AND METHODS: Fifteen patients with Parkinson's disease and orthostatic hypotension and 13 patients with Parkinson's disease without orthostatic hypotension were studied. We compared brain perfusion image between the two groups by 3D-SSP. RESULTS: Bilateral anterior cingulate gyrus perfusion of the patients with orthostatic hypotension was significantly decreased compared to that of the patients without orthostatic hypotension. CONCLUSIONS: The disorder of anterior cingulate gyrus may participate in the autonomic failure in Parkinson's disease.

Clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease.

BACKGROUND: No method for the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease (sCJD) has been established except for pathologic examination. OBJECTIVE: To identify a reliable marker for the clinical diagnosis of MM2-type sCJD. METHODS: CSF, EEG, and neuroimaging studies were performed in eight patients with MM2-type sCJD confirmed by neuropathologic, genetic, and western blot analyses. RESULTS: The eight cases were pathologically classified into the cortical (n = 2), thalamic (n = 5), and combined (corticothalamic) (n = 1) forms. The cortical form was characterized by late-onset, slowly progressive dementia, cortical hyperintensity signals on diffusion-weighted imaging (DWI) of brain, and elevated levels of CSF 14-3-3 protein. The thalamic form showed various neurologic manifestations including dementia, ataxia, and pyramidal and extrapyramidal signs with onset at various ages and relatively long disease duration. Characteristic EEG and MRI abnormalities were almost absent. However, all four patients examined with cerebral blood flow (CBF) study using SPECT showed reduction of the CBF in the thalamus as well as the cerebral cortex. The combined form had features of both the cortical and the thalamic forms, showing cortical hyperintensity signals on DWI and hypometabolism of the thalamus on [18F]2-fluoro-2-deoxy-d-glucose PET. CONCLUSION: For the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease, cortical hyperintensity signals on diffusion-weighted MRI are useful for the cortical form and thalamic hypoperfusion or hypometabolism on cerebral blood flow SPECT or [18F]2-fluoro-2-deoxy-d-glucose PET for the thalamic form.

A case of idiopathic spinal epidural lipomatosis presented with radicular pain caused by compression with enlarged veins surrounding nerve roots.

OBJECTIVE: To report a case of idiopathic spinal epidural lipomatosis (SEDL) presented with unique radicular pain most likely caused by enlarged veins surrounding nerve roots. PATIENT: A 26-year-old male presented with radicular pain of the right T6-T7 area. He also showed Becker's nevus in the corresponding area. CT myelography and magnetic resonance imaging revealed epidural lipomatosis posterior to T4-T8 of the spinal cord. Surgical removal of adipose tissue and a hemilaminectomy of T4-T7 were performed and resulted in relief of the radicular pain. CONCLUSIONS: Lipomatosis was histologically confirmed and surrounded by enlarged veins. These abnormally enlarged veins compressed the nerve roots and were thought to cause radicular pain. Also, Becker's nevus of this case seems to have some relationship with SEDL.

[A case of SLE presenting the features of antiphospholipid antibody syndrome during a treatment for complicated cryptococcal meningitis].

A 39-year-old woman had developed systemic lupus erythematosus(SLE) at the age of 29. She had a long history of immunosuppressant therapies such as corticosteroid. On admission, she presented a headache due to the cryptococcal meningitis which was confirmed by lumbar puncture. Combined medications of amphotericin B and fluconazole were not effective, and combined amphotericin B and flucytosine were replaced. Prednisolone and methotrexate had been tapered gradually. Fifty days after the initial treatment for meningitis Cryptococcal neoformans was not observed in the cerebrospinal fluid. Sixty days after the treatment, thrombocytopenia was observed with positive lupus anticoagulant and anticardiolipin antibody. Following which, thrombophlebitis occurred in the left brachium. We suggest that the provoked pathoimmunological reaction such as antiphospholipid antibody syndrome during the treatment for meningitis needs to be cared during the course of SLE.

Severe brain atrophy in a case of thalamic variant of sporadic CJD with plaque-like PrP deposition.

A 30-year-old woman presented with ataxic gait and progressive mental deterioration, and 3 years later developed myoclonus in the limbs. Subsequently, she lapsed into an akinetic state and died more than 6 years after the onset of disease. The brain weighed 670 g, and preferential degeneration was found in the medial thalamus and the inferior olivary nucleus. In the cerebrum and cerebellum, gliosis and neuronal depletion were only mild and disintegration of the parenchymal structures was inconspicuous, despite pronounced atrophy. The patient had methionine homozygosity at codon 129 of the PrP gene and protease-resistant PrP type 2 in the brain. On PrP immunostaining, plaque-like deposits were detected in the cerebral and cerebellar cortices. Severe brain atrophy such as in the present case has never been described in the thalamic variant of sporadic CJD.

[A case of inflammatory myopathy worsened by miscarriage with autoimmune disorder-associated disease].

The patient was 42-year-old woman who had exhibited elevated levels of serum creatine kinase(CK) and intermittent weakness of proximal muscles since her thirties. She had a history of palmoplantar pustulosis, Mondor's disease and recurrent miscarriages. Basedow's disease, which had been treated with antithyroid drugs since 37 years of age, recurred during the fourth pregnancy. After the pregnancy was terminated in the sixth week, weakness and grasp pain in the proximal muscles developed. The biopsy of biceps brachii muscle showed necrosis and reconstruction of muscle fibers with equivocal inflammatory cells, which was compatible with the findings for inflammatory myopathy such as polymyositis(PM). She was treated with prednisolone and the weakness and grasp pain in the proximal muscles were resolved. PM beginning during a woman's reproductive period is rare, and few studies have examined the association between PM and pregnancy. In this case, pregnancy and her past diseases were considered to be linked to an autoimmune abnormality that might have contributed to the inflammatory myopathy.

[A case of recurrent ischemic attacks: consecutive diffusion-weighted magnetic resonance imaging].

A 61-year-old man with recurrent ischemic attacks was examined by diffusion-weighted MRI (DWI). He had reversible right hemiparesis and dysarthria five times during admission. DWI was obtained on the first two attacks, the last attack and four days after the last attack. The first two attacks were clinically diagnosed as transient ischemic attack (TIA), and the last attack was cerebral infarction with symptoms persistent for one week with Babinski's sign. In the first and last images the apparent diffusion coefficient (ADC) declined to approximately 80% of the corresponding area. We conclude that different images showed TIA with ADC declining, TIA without ADC declining, the hyperacute phase of cerebral infarction before ADC declining, and cerebral infarction after ADC declining. Consecutive DWIs were helpful to understand the character of recurrent ischemic attacks.

[Cerebral infarction presenting pure motor monoparesis: diagnosis by diffusion-weighted MR imaging].

We studied 10 patients with acute ischemic cerebrovascular disorders presenting paralysis confined to one limb, unaccompanied by sensory signs(pure motor monoparesis, PMM) on diffusion-weighted MR imaging(DWI). DWI revealed fresh ischemic lesions in all patients, except for 2 cases of transient ischemic attack. On DWI, acute infarction in multiple lesions was identified, and small superficial lesions were clearly described. Superficial lesions were seen in 4 patients, and deep lesions were also seen in 4 patients. DWI is useful for lesion analysis in cerebral infarction with PMM.

Genetic studies in Parkinson's disease with an alpha-synuclein/NACP gene polymorphism in Japan.

Dinucleotide repeat polymorphism has been observed in the promoter of the alpha-synuclein (alpha-SYN)/NAC precursor protein (NACP) gene. Alpha-SYN/NACP allele 3 (described by Xia et al. (Ann. Neurol., 40 (1996) 207), equivalent to allele 1 described by Krüger et al. (Ann. Neurol. 45 (1999) 611) is reported to be significantly more frequent among patients with sporadic Parkinson's disease (sPD) than controls. In this study, we genotyped the same alpha-SYN/NACP polymorphism in Japanese sPD patients and healthy controls, but found that any aliele showed no significant difference between the two groups.

Clinical efficacy and safety of donepezil on cognitive and global function in patients with Alzheimer's disease. A 24-week, multicenter, double-blind, placebo-controlled study in Japan. E2020 Study Group.

This study evaluated efficacy and safety of donepezil hydrochloride (donepezil) at 5 mg/day in patients with mild to moderately severe Alzheimer's disease for 24 weeks in a double-blind, placebo-controlled comparative trial. In this study, 268 patients were enrolled and 39 of these (15%) were withdrawn. In the evaluable population of efficacy, Protocol-Compatible (PC) analyzed patients (n = 228), better effects than that of placebo were confirmed using two primary efficacy measures: a cognitive performance test, the Japanese version of the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-J cog, p = 0.003) and a clinical global assessment, the Japanese version of the Clinical Global Impression of Change (J-CGIC, p = 0.000). The superiority of donepezil was also shown by secondary measures: the Sum of the Boxes of the Clinical Dementia Rating (CDR-SB), the Mental Function Impairment Scale (MENFIS) and the caregiver-rated modified Crichton scale (CMCS). The same results were obtained in the intention-to-treat (ITT) analysis (n = 263). The incidence of drug-related adverse events was 10% (14/136) in the donepezil and 8% (10/131) in the placebo group; no significant difference was seen between the two groups. The main adverse events were gastrointestinal symptoms, and these were almost all mild, and they all disappeared with continued administration or temporary discontinuation of donepezil. These results indicate that the donepezil appears to be effective and well tolerated in patients with mild to moderately severe Alzheimer's disease.

Deep white matter lesions on MRI, and not silent brain infarcts are related to headache and dizziness of non-specific cause in non-stroke Japanese subjects.

OBJECTIVE: Silent or asymptomatic cerebrovascular disease is believed to be an important risk factor for symptomatic stroke and vascular dementia. Although non-specific complaints such as mild to moderate headache and/or dizziness may also be caused by silent stroke, which remains a topic of controversy. METHODS: To investigate the relationship between silent brain infarcts and non-specific complaints, we assessed findings on magnetic resonance images using a common protocol in the following three groups of subjects; Group 1:78 subjects with non-specific complaints, Group 2:47 subjects with vascular risk factors, and Group 3:75 normal subjects without any subjective complaints or vascular risk factors. In addition to silent stroke, deep white matter lesions on MRI were also evaluated. All subjects were recruited from 12 institutes of the study group located at various parts of Japan. RESULTS: Silent brain infarcts were demonstrated in 44%, 43%, and 20% of subjects in Groups 1, 2, and 3, respectively. In Group 1, the average number of infarcts per individual who had silent brain infarction was 1.8, which was significantly fewer than 3.8 in Group 2 or 3.5 in Group 3 (p<0.0167). White matter lesions were found in 68%, 49%, and 11% in Groups 1, 2, and 3, respectively, indicating that non-specific complaints are more closely related to deep white matter lesions than to silent infarct lesions. Such white matter lesions were found more frequently in subjects with depressive state than in non-depressed subjects (67% vs. 39%, p=0.0155). CONCLUSION: The present results suggest that deep white matter lesions, rather than silent brain infarcts, appear to be important in producing headache and/or dizziness of non-specific cause and also to be related to the depressive state.

A single nucleotide polymorphism of dopamine transporter gene is associated with Parkinson's disease.

We identified two polymorphisms out of all coding regions of the dopamine transporter gene. One existed in exon 9 (1215A/G) and another in exon 15 (1898T/C). The 1215G was significantly less frequent among patients with Parkinson's disease than the controls. Although the polymorphism caused no amino acid substitution, we concluded that it was associated with decreasing the susceptibility to Parkinson's disease through mechanisms other than the protein function of dopamine transporter.

Cerebral white matter lesions are not associated with apoE genotype but with age and female sex in Alzheimer's disease.

Cerebral white matter lesions, such as leukoaraiosis, may be a result of damage from cerebral ischaemia, and may also be associated with the degenerative process in Alzheimer's disease. The apolipoprotein epsilon4 (apoepsilon4) genotype is a genetic risk factor for both Alzheimer's disease and ischaemic brain damage through acceleration of atherosclerosis. The aim was to determine whether apoepsilon4 may be related to the formation of cerebral white matter lesions in Alzheimer's disease. The association of apoE genotype, sex, age, and the presence of several vascular risk factors, with the presence of white matter lesions in 55 patients clinically diagnosed with Alzheimer's disease was investigated. The cerebral white matter lesions were identified by T2 weighted MRI and classified on a 4 grade scale from no lesion to diffuse lesion. The odds ratio (OR) of the factors mentioned above to the presence of white matter lesions was determined and tested by Fisher's exact test. The association of the lesion grades with these factors was analysed by non-parametric tests. The apoE 4 genotype was strongly associated with Alzheimer's disease (p=0.0001), but not associated with the presence or the degree of cerebral white matter lesions in Alzheimer's disease (OR=1.09, p>0.99). Aging (>70 years old) was a significant risk factor for white matter lesions (OR=7.2, p=0.0006) and age was significantly correlated with the lesion (p=0.0075). The OR of female sex to the lesion grades was 2.89 (p=0.084) and the lesion grade of female sex was significantly higher than that of the male sex (p=0.047). Other vascular risk factors were not significantly associated with the presence of white matter lesions. These findings suggest that there is a sex difference in white matter pathology in Alzheimer's disease.

[A case of acute motor sensory axonal polyneuropathy after Haemophilus influenzae infection].

A 47-year-old woman developed consciousness disturbance, and experienced hallucinations while traveling abroad, and then went into critical condition. She was placed in the critical care unit, and had flaccid tetraparesis requiring mechanical ventilation. Haemophilus influenzae was cultured from the sputum. The level of protein of the cerebrospinal fluid was elevated to 114 mg/dl, nerve conduction study showed findings of pure axonal damage, and the sural nerve biopsy revealed severe axonal degeneration. She improved gradually by plasma exchange. The diagnosis of acute motor sensory axonal polyneuropathy (AMSAN) based on autoimmune mechanism was made. We speculate that H. influenzae infection may have elicited AMSAN in this case.

[An autopsy case of intracranial T cell type malignant lymphoma with fluctuating neuropsychological symptoms].

A 59-year-old man was admitted to the hospital due to leg edema. He had multiple sclerosis-like episodes of transient diplopia at the age of 36 years and spastic paraplegia at the age of 38. After admission he showed various fluctuating neuropsychological symptoms (disorientation, hallucination, apraxia, aphasia) and cranial nerve palsy. Magnetic resonance imaging revealed abnormal signal intensity in the right thalamus and deep white matter. The patient was diagnosed as having malignant lymphoma and treated with steroid therapy and chemotherapy. Although partial improvement of clinical findings was observed, recurrent cerebral hemorrhage followed. Autopsy findings revealed perivascular infiltration of T cells in the brain, spinal cord and other general organs.