Presynaptic and postsynaptic nigrostriatal dopaminergic functions in multiple system atrophy.

A simultaneous evaluation of presynaptic and postsynaptic dopaminergic positron emission tomography markers, the dopamine transporters and the dopamine D2-like receptors, was performed in eight patients with parkinsonian phenotype of multiple system atrophy. Both presynaptic and postsynaptic markers were revealed to have declined in such a manner that they kept strong positive correlation throughout the striatum of all patients, suggesting that the degeneration process in the striatum may involve the entire structure of the dopaminergic synapse. In two L-3,4,dihydroxyphenyl-alanine-responsive cases, the balance of decline in two markers was relatively shifted to presynaptic dominant side. Correlative positron emission tomography study of presynaptic and postsynaptic dopaminergic function may be useful for the diagnosis of multiple system atrophy and to understand the mechanisms of its temporal L-3,4,dihydroxyphenyl-alanine responsiveness.

[Late onset hemiparkinsonism-hemiatrophy syndrome: a case report].

Hemiparkinsonism-hemiatrophy syndrome (HPHA) is a rare form of parkinsonism, characterized by unilateral parkinsonism, ipsilateral body atrophy and early age of onset. We report a 59-year-old woman with hemiatrophy of her face and upper limb on the left side presenting progressive hemiparkinsonism. Most of the HPHA patients have early age of onset, however, HPHA patients with age of onset over 50 years old have been reported. The clinical features of CBD are partly similar to those of HPHA, therefore it is important to consider HPHA as differential diagnosis of CBD even if the onset is late. In our patient, hemiatrophy was useful to differentiate HPHA from CBD. In previous reports, there was a difference between the dopamine D2 receptor binding capacity of CBD and that of HPHA. While the dopamine D2 receptor binding capacity of CBD was decreased asymmetrically, that of HPHA was not decreased. The PET finding of our patient revealed that asymmetrical reduction of [11C]-CFT uptake, meaning unilateral dopaminergic presynaptic hypofunction. However, [11C]-raclopride uptake, which assesses dopamine D2 receptor binding capacity, was normal. These PET findings are consistent with previous reports on HPHA. In our patient, hemiatrophy and PET findings were useful to diagnose HPHA.

Constant and severe involvement of Betz cells in corticobasal degeneration is not consistent with pyramidal signs: a clinicopathological study of ten autopsy cases.

This report concerns a clinicopathological study of three additional patients with corticobasal degeneration (CBD), described here for the first time, and a clinicopathological correlation between pyramidal signs and upper motor neuron involvement, in ten autopsy cases of CBD, including seven cases reported by us previously. We investigated pyramidal signs, including hyperreflexia, Babinski sign, and spasticity, and involvement of the primary motor cortex and pyramidal tract, focusing on the astrocytosis of the fifth layer of the primary motor cortex. Pyramidal signs were observed in six (60%) of the ten cases. Hyperreflexia was evident in six patients (60%), with spasticity being observed in three patients (30%). Loss of Betz cells associated with prominent astrocytosis and presence of ballooned neurons in the fifth layer of the primary motor cortex was observed in all ten cases. In all cases, involvement of the pyramidal tract was obvious in the medulla oblongata, without involvement of the pyramidal tract in the midbrain. Constant and severe involvement of the fifth layer of the primary motor cortex, including the Betz cells, has not previously been reported in CBD. We suggest that the pyramidal signs in CBD have been disregarded.

A clinical and genetic study in a large cohort of patients with spinocerebellar ataxia type 6.

In order to clarify the clinical and genetic features of SCA6, we retrospectively analyzed 140 patients. We observed an inverse correlation between the age of onset and the length of the expanded allele, and also between the age of onset and the sum of CAG repeats in the normal and the expanded alleles. The ages of onset of four homozygous patients correlated better with the sum of CAG repeats in both alleles rather than with the expanded allele calculated from heterozygous SCA6 subjects. Clinically, unsteadiness of gait was the main initial symptom, followed by vertigo and oscillopsia, and cerebellar signs were detected in nearly 100% of the patients. In contrast, extracerebellar signs were relatively mild and infrequent. The results of neuro-otological examination performed in 22 patients suggested the purely cerebellar abnormalities of ocular movements in nature. There was a close relationship between downbeat positioning nystagmus (DPN) and positioning vertigo, which became more common in the later stage. We conclude that total number of CAG repeat-units in both alleles is a good parameter for assessment of age of onset in SCA6 including homozygous patients. In addition, clinical and neuro-otological examinations suggested that SCA6 is a disease with predominantly cerebellar dysfunction.

[Parkinson disease with dementia--responsible locus for dementia].

Responsible locus for dementia in Parkinson disease (PD) was investigated. Serial 1,395 autopsy cases were studied for the combined pathology of PD and Alzheimer disease (AD). Following the one-year rule by the first Consensus Guidelines, definite AD pathology was quite rare in PD with dementia (PDD) but common in dementia with Lewy bodies (DLB) . Plaque-dominant senile changes apparently enhanced neocortical Lewy-body pathology in both the conditions. About the hypometabolism in the visual cortex of PDD, a 66-year old man presented with fluctuation in hallucination commensurate with fluctuating hypometabolism. Considering the paucity in pathological changes of the visual cortex, this hypometabolism may represent functional impairment in the fiber connection. Comparative pathological studies with PD and PDD were carried out. Only one case of a 48-year-old woman, who unexpectedly died of heart failure, was free from cognitive decline, and did not show limbic and neocortical involvement. Another case of a 75-year old man with MCI presented with the similar pathology. All other cases showed clinical documentation of cognitive impairment and limbic and neocortical pathological involvement. Thus, the combination of prospective clinical and radiological studies and retrospective pathological studies (dynamic neuropathology) may be essential to investigate a role of the basal-forebrain cholinergic system.