Arakawa K

A novel autosomal dominant spinocerebellar ataxia (SCA16) linked to chromosome 8q22.1-24.1.

Objective: To characterize a distinct form of autosomal dominant cerebellar ataxia (ADCA) clinically and genetically. Background: ADCAs are a clinically, pathologically, and genetically heterogeneous group of neurodegenerative disorders. Nine responsible genes have been identified for SCA-1, -2, -3, -6, -7, -8, -10, and -12 and dentatorubral-pallidoluysian atrophy (DRPLA). Loci for SCA-4, -5, -11, -13, and -14 have been mapped. Methods: The authors studied a four-generation Japanese family with ADCA. The 19 members were enrolled in this study. The authors performed the mutation analysis by PCR and a genome-wide linkage analysis. Results: Nine members (five men and four women) were affected. The ages at onset ranged from 20 to 66 years. All affected members showed pure cerebellar ataxia, and three patients also had head tremor. Head MRI demonstrated cerebellar atrophy without brain stem involvement. The mutation analysis by PCR excluded diagnoses of SCA-1, -2, -3, -6, -7, -8, and -12 and DRPLA. The linkage analysis suggested linkage to a locus on chromosome 8q22.1-24.1, with the highest two-point lod score at D8S1804 (Z = 3.06 at θ = 0.0). The flanking markers D8S270 and D8S1720 defined a candidate region of an approximately 37.6-cM interval. This candidate region was different from the loci for SCA-4, -5, -10, -11, -13, and -14. Conclusion: The family studied had a genetically novel type of SCA (SCA-16).

Familial Creutzfeldt-Jakob disease with D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia.

Fatal familial insomnia (FFI) is a prion disease clinically characterised by progressive insomnia and dysautonomia, and associated with an aspartic acid to asparagine mutation at the codon 178 (D178N) of the prion protein gene ( PRNP ).1 This mutation is also associated with familial Creutzfeldt-Jakob disease (CJD). These phenotypes have been held to depend on the polymorphism at the codon 129. FFI and CJD phenotypes are associated with methionine (129M) and valine (129V) polymorphisms, respectively.2 However, the diverse phenotypes can be associated with D178N-129M genotype.3 4 We here report on a Japanese family with D178N-129M genotype presenting cerebellar ataxia without overt insomnia. Pedigree of the family and genotypes. (A) Pedigree of the family. Squares, males; circles, females; triangles, either sex (to protect the confidentiality of the family, the sexes of these people are not shown). Filled symbols, affected; shaded symbols, genotype only examined; slashed symbols, deceased; numbers, ages of onset. (B) Tth 111I and Nsp I restriction analyses of the 848 bp open reading frame of PRNP. The Tth 111I-non-digested band of 848 bp indicates D178N mutation. The Nsp I-non-digested band of 502 bp indicates 129V polymorphism and the 427 bp …

Clustering of three cases of Creutzfeldt-Jakob disease near Fukuoka City, Japan

ABSTRACT During a 4‐month period we encountered three patients with Creutzfeldt‐Jakob disease (CJD). All lived in a limited area near Fukuoka City in Japan. Such a significantly close spatial and temporal clustering of cases suggests exposure to a common CJD infectious agent. Except for dental‐related treatments, there were no evident causative agents common to these three patients.

Parvocellular and magnocellular visual processing in spinocerebellar degeneration and Parkinson's disease: an event-related potential study.

OBJECTIVE We recorded event-related potentials (ERPs) using appropriate visual stimuli to establish a non-invasive method that separately investigates the parvocellular (P) and magnocellular (M) visual functions, and to evaluate the visual function in spinocerebellar degeneration (SCD) and Parkinsons disease (PD). METHODS Eight SCD and 10 PD patients were compared with 11 age-matched control subjects. In the P-task, subjects were required to discriminate equiluminant red (frequent) and green (rare) random dots. In the M-task, moving random dots on a rotating cylinder (frequent) and those moving irregularly (rare) were discriminated. RESULTS Control subjects showed an endogenous positive component at 400 ms (P400(p)) with an early exogenous negative potential (N160(p)) in the P-task. In the M-task, N160(m) and P400(m) were recorded. A deuteranope lacked P400(p) with normal P400(m). In SCD, P400(p) latency and N160(p)-P400(p) interval were increased with normal N160(p) latency. N160(m) latency was also increased while N160(m)-P400(m) interval was normal. In PD, there were no significant changes in the P-task but P400(m) latency was increased with normal N160(m) latency. CONCLUSIONS SCD patients may have not only abnormal higher processing in the P-pathway but abnormal fundamental processing in the M-pathway. PD may have impaired higher processing of the M-pathway with the preserved P-function.

Ocular dominancy in conjugate eye movements at reading distance.

We recorded conjugate eye movements to elucidate whether ocular dominancy was present at reading distance in 21 normal volunteers with the right-handedness by using a video-oculographic (VOG) measurement. This included the velocity of smooth pursuits, and the latency and velocity of saccades. We defined the dominant eye for each subject by means of the near-far alignment test and 20 subjects showed the right dominant eyes. Although the ocular dominancy was not found in the velocity of smooth pursuit and vertical saccades, the velocity of horizontal saccades in the dominant eyes was faster than that in the non-dominant eyes. These results suggest that the dominant eye is functionally activated prior to non-dominant eye in horizontal saccades at reading distance, which thus indicates the functional dominancy of the dominant eye in conjugate eye movements.

The effect of spatial frequency on chromatic and achromatic steady-state visual evoked potentials

OBJECTIVE Little is known about the physiological properties of the major components of steady-state visual evoked potentials (VEPs). Based on the hypothesis that isoluminant color and high contrast pattern differentially activate the parvo- and magnocellular pathways, we studied difference in spatial frequency function between chromatic and achromatic VEPs to sinusoidal gratings. METHODS Steady-state VEPs to isoluminant chromatic (red-green) and high contrast (90%) achromatic (black-white) sinusoidal gratings with nine spatial frequencies (0.5 to 8.0 cycles/degrees (cpd)) at 4 Hz (8 reversals/s) were recorded in 13 normal subjects. VEPs were Fourier analyzed to obtain phase and amplitude of the second (2F) and fourth (4F) harmonic responses. RESULTS The 2F amplitude of chromatic VEPs decreased above 4.0 cpd in a low-pass function while that of achromatic VEPs showed a band-pass function with a peak at 4.0 cpd. The 4F amplitude of chromatic VEPs was not affected significantly by spatial frequency whereas that of achromatic VEPs exhibited a high-pass function. The phases of 2F and 4F showed a non-monotonic function of spatial frequency in both chromatic and achromatic stimuli with peaks at middle spatial frequencies. CONCLUSION Chromatic and achromatic visual stimuli differently affected 2F and 4F components, which thus suggests that 2F and 4F components are generated from different neuronal subgroups largely in the parvocellular pathway.

Electrophysiological correlates of associative visual agnosia lesioned in the ventral pathway

Visual agnosia has been well studied by anatomical, neuropsychological and neuroimaging studies. However, functional changes in the brain have been rarely assessed by electrophysiological methods. We carried out electrophysiological examinations on a 23-year-old man with associative visual agnosia, prosopagnosia and cerebral achromatopsia to evaluate the higher brain dysfunctions of visual recognition. Electrophysiological methods consisted of achromatic, chromatic and category-specific visual evoked potentials (CS-VEPs), and event-related potentials (ERPs) with color and motion discrimination tasks. Brain magnetic resonance imaging revealed large white matter lesions in the bilateral temporo-occipital lobes involving the lingual and fusiform gyri (V4) and inferior longitudinal fasciculi due to multiple sclerosis. Examinations including CS-VEPs demonstrated dysfunctions of face and object perception while sparing semantic word perception after primary visual cortex (V1) in the ventral pathway. ERPs showed abnormal color perception in the ventral pathway with normal motion perception in the dorsal pathway. These electrophysiological findings were consistent with lesions in the ventral pathway that were detected by clinical and neuroimaging findings. Therefore, CS-VEPs and ERPs with color and motion discrimination tasks are useful methods for assessing the functional changes of visual recognition such as visual agnosia.

Middle latency auditory-evoked potentials in myotonic dystrophy: relation to the size of the CTG trinucleotide repeat and intelligent quotient

OBJECTIVE Major components of MLAEPs are thought to originate in the temporal lobe. Absence of the Pb potential has been demonstrated in MLAEPs in Alzheimers disease and demented Parkinsons disease patients. To validate usefulness of middle latency auditory-evoked potentials (MLAEPs) in evaluating the central nervous system (CNS) involvement of myotonic dystrophy (MyD). METHODS MLAEPs were recorded in eight patients with MyD and nine normal control subjects. In the patient group, the size of the CTG triplet repeat expansion within the dystrophia myotonica protein kinase (DMPK) gene and the revised Wechsler Adult Intelligence Scale (WAIS-R) were also assessed. RESULTS The latency of the Nb potential showed a significant correlation with the size of the CTG repeat expansion (r=0.734, P=0.036). The Pb latency also tended to prolong according to CTG amplification (r=0.644, P=0.087). The amplitudes of Na and Pa significantly increased compared with those of normal control subjects (P=0.024 and 0.016, respectively). However, they did not correlate with IQ or CTG amplification. CONCLUSIONS Abnormal MLAEPs may indicate CNS involvement in MyD. Although the precise generating mechanisms of Nb are unclear, the correlation of Nb latency with CTG amplification suggests that MLAEPs can reflect the extent of genetic abnormality.

Different effects of cholinergic agents on responses recorded from the cat visual cortex and lateral geniculate nucleus dorsalis.

We investigated the effect of cholinergic agents on the cat visual evoked potentials (VEPs) recorded from the primary visual cortex (V1) and lateral geniculate nucleus dorsalis (LGNd) to determine on which level of the visual pathway the cholinergic system acts. VEPs to the alternation of 0.1 cycles per degree sinusoidal gratings at 1 and 4 Hz were recorded from N2O-anesthetized cats directly from the surface of V1 and LGNd. The depth of recording in LGNd was determined by the site where the maximal response was obtained by 1 Hz stimulation. VEPs to 4 Hz stimulation, which showed sinusoidal waveforms and were analyzed by fast Fourier transforms, were used as indicators for modulation by cholinergic agents. Physostigmine, an acetylcholinesterase inhibitor, 0.7 mg/kg i.v., suppressed the amplitude of the responses more at V1 (suppression ratio: mean +/- SD, 85.4 +/- 9.3%) than at LGNd (32.4 +/- 30.7%) (P < 0.05). Conversely, scopolamine, a muscarinic receptor blocker, 0.7 mg/kg i.v., increased the amplitude of the responses more at V1 (enhancement ratio: mean +/- SD, 60.3 +/- 22.3%) than at LGNd (-22.2 +/- 22.5%) (P < 0.05). These results indicate that the V1 changes reflect a direct cortical cholinergic effect, probably by modulating the cholinergic projection from the nucleus basalis of Meynert to V1.

Adult-onset hereditary sensory and autonomic neuropathy accompanied by anosmia but without skin ulceration

We report a novel type of hereditary sensory and autonomic neuropathy (HSAN) with adult onset in a Japanese family. One male and 2 females of 6 siblings were affected. They developed anosmia initially at the ages of 20–50 years, followed by anhidrosis and sensory loss. Skin ulceration was absent. Both superficial and deep sensation were impaired in the most distal parts of all 4 limbs. Orthostatic hypotension was present in all patients. This is a unique subtype of HSAN distinct from the HSAN I–V described by Dyck.