Misuzu Saiki

Cardiac 123I-MIBG scintigraphy can assess the disease severity and phenotype of PD

OBJECTIVE Cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigraphy studies of patients with idiopathic Parkinsons disease (PD) found decreased uptake. Whether this decrease is associated with clinical severity as assessed by the Unified Parkinsons Disease Rating Scale (UPDRS) and the phenotypes of PD has not been determined. METHODS Cardiac MIBG scintigraphy was performed on 34 patients with PD, 7 with multiple system atrophy (MSA), 4 with dementia with Lewy bodies (DLB), and 11 normal controls (NCs). Early and delayed MIBG heart/mediastinum (H/M) ratios were evaluated. PD severity was assessed by the Hoehn and Yahr (H-Y) stage and UPDRS. Patients were grouped in two phenotypes, tremor and postural instability gait difficulty (PIGD)-dominant groups based on UPDRS components. Associations between MIBG uptake and age at onset, UPDRS, and disease phenotype were analyzed in each group. RESULTS The early H/M ratio was significantly lower in patients with PD (1.45+/-0.207) than in the NCs (2.08+/-0.231), and in those with MSA (1.99+/-0.284), but not in those with DLB (1.29+/-0.0435). The delayed H/M ratio for PD (1.33+/-0.276) also was significantly decreased as compared to the ratios for NCs (2.17+/-0.286) and MSA (2.16+/-0.414) but not DLB (1.16+/-0.0949). The early H/M ratio was significantly correlated with both UPDRS score and age at onset, whereas the delayed H/M ratio only was significantly correlated with age at onset. The PIGD-dominant group had significantly higher UPDRS scores and lower H/M ratios than the tremor-dominant group. CONCLUSION Cardiac MIBG scintigraphy can be used to differentiate PD from MSA and NC, and to determine the disease severity and phenotypes of PD.

Mutation in the CHAC gene in a family of autosomal dominant chorea–acanthocytosis

Writ e Click is restricted to comments about studies published in Neurology ® within the past 8 weeks. The submission below represents an exception because it addresses a genetic sequencing error published in Neurology in 2003. In addition, these Writ e Click submissions will be available as open access to all readers in an effort to further publicize the Correction. In 2003, Saiki et al.1 reported an autosomal dominant transmission of chorea-acanthocytosis (ChAc) that constituted a significant challenge to the generally …

Chorea-acanthocytosis associated with Tourettism.

We report on a case of Chorea‐acanthocytosis (ChAc) in association with Tourettism that consisted of motor and vocal tics, attention deficit–hyperactivity disorder, and obsessive–compulsive disorder in addition to the typical symptoms of ChAc. The subject was compared with his elder sister who had the same disease but milder clinical profile and neuroradiological findings. The [18F]‐2‐fluoro‐2‐deoxyglucose positron emission tomography (FDG‐PET) findings did not explain the differences in symptomatology between the patient and his sister, although they may have correlated with severity.

Varicose veins associated with CADASIL result from a novel mutation in the Notch3 gene.

No genetically diagnosed cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) pedigrees with venous insufficiency have been described. In a CADASIL pedigree with varicose veins, the authors have identified a novel heterozygous mutation in the 3′ splice acceptor site of intron 15 of the Notch3 gene. This, based on mRNA analysis, resulted in skipping of exon 16 including eight cysteine residues of EGF-like repeats.

Primary skeletal muscle involvement in chorea-acanthocytosis.

Chorea‐acanthocytosis (ChAc) is a hereditary disease characterized by involuntary movements and amyotrophy with elevation of serum creatine kinase. Although skeletal muscle involvement in ChAc has been suggested, the mechanism remains unclear. To investigate chorein abnormalities of the skeletal muscles of ChAc patients with an apparently heterozygous VPS13A mutation compared with those of other hereditary choreic diseases, we performed histological and immunohistochemical studies of the skeletal muscles from 3 ChAc, 1 Huntingtons disease (HD), 1 McLeod syndrome (MLS), and 1 normal control (NC) with 2 originally generated anti‐chorein antibodies. Chorein immunoreactivities in HD, MLS, and NC were found linearly along the sarcolemma and appeared as speckles in the sarcoplasma, but those in ChAc were uneven and discontinuous along the sarcolemmas and increased in the sarcoplasma especially in type I fibers. This histological observation suggests chorein abnormalities of skeletal muscles might be associated with primary involvement of skeletal muscles in this disorder.

Effect of a paraneoplastic cerebellar degeneration-associated neural protein on B-myb promoter activity.

In this study, we have shown that a paraneoplastic cerebellar degeneration (PCD)-associated antigen, pcd17, binds to a cell cycle-related protein, MRG15. MRG15 derepresses the E2F-responsive B-myb promoter. The pcd17 antigen inhibits the derepression of the B-myb transcriptional activity by MRG15, and, as a result, pcd17 represses the promoter. Delivery of anti-Purkinje cell antibodies (anti-Yo) into the cells inhibits the repression of B-myb promoter activity by pcd17. Because derepression of the B-myb promoter has been implicated in neuronal death, the results suggest the possible role of the antibodies in the pathogenesis of PCD.

Rostral lateral pontine infarction: Neurological/topographical correlations

The authors correlated neurologic features of rostral lateral pontine infarct (rLPI) with lesion location on MRI. rLPI is a motor-sensory stroke presenting as crural monoparesis or crural dominant hemiparesis and segmental superficial or deep sensory disturbances. The dorsolateral pontine base causes crural paresis without supranuclear facial palsy.

Neurological deficits are associated with increased brain calcinosis, hypoperfusion, and hypometabolism in idiopathic basal ganglia calcification

We report two familial cases of idiopathic basal ganglia calcification. A 60‐year‐old proband with choreoathetosis, dysarthria, and cognitive decline showed more extensive brain calcinosis, hypoperfusion, and hypometabolism than did his asymptomatic 82‐year‐old mother. The mother had no frontal lobe calcinosis but basal ganglia and dentate nucleus depositions were detectable. Perfusion neuroimaging, however, was normal in the asymptomatic mother and abnormal in the clinically impaired proband. The presence of calcinosis cannot be used as an index of neurological impairment but the extent of calcinosis and reduction in perfusion and metabolism may be useful for separating symptomatic from asymptomatic subjects with IBGC. These findings suggest that an interruption of neuronal circuitry may cause neurological deficits. The degree of neurological deficits may correlate with the severity of calcinosis and the reduction of perfusion and metabolism.