Kenji Kuroda

Cervical and Intracranial Atherosclerosis and Silent Brain Infarction in Japanese Patients with Coronary Artery Disease

Purpose: To investigate the prevalence of cervical and intracranial atherosclerosis and silent brain infarction in patients with coronary artery disease (CAD). Methods: Cervical and intracranial atherosclerotic lesions on magnetic resonance angiography (MRA) and silent brain infarctions on magnetic resonance imaging (MRI) were investigated in comparison with the findings of coronary angiography in 133 consecutive patients with CAD. Results: The mean severity scores of cervical and intracranial MRA lesions were significantly higher in the three-vessel CAD (0.40 and 0.53, respectively) than in the zero-vessel CAD group (0.04 and 0.11). The mean scores of the maximal size and multiplicity of MRI lesion were also significantly greater in the two-vessel (1.00 and 1.44) and three-vessel CAD (0.94 and 1.26) than in the zero-vessel CAD group (0.27 and 0.50). The incidence of MRA lesion was markedly higher in patients with brain MRI lesion than in those without (51.1 vs. 6.5%). Conclusions: Serious coronary artery lesions were commonly accompanied by latent atherosclerotic lesions in the cervical and intracranial arteries besides silent brain infarction in patients with CAD.

Nineteen CAG repeats of the SCA6 gene in a Japanese patient presenting with ataxia.

Sirs: Spinocerebellar ataxia type 6 (SCA6), an autosomal dominant neurodegenerative disease characterized by slowly progressive cerebellar ataxia, has been shown to be due to expansion of the number of CAG repeats in the human α1A voltagedependent calcium channel subunit gene on chromosome 19p13 [11]. The increases in the CAG repetitions within the SCA6 gene are small and close to those of normal subjects. According to previous reports, the pathological range of CAG repeats in the SCA6 gene is 20 or more, and the normal range is 18 or less [1, 2, 4–10]. Interestingly, four individuals who were 70–75 years of age with 19 CAG repeats of SCA6 gene have been reported as neurologically normal [3]. We present a 50-year-old patient with 19/7 CAG repeats of the SCA6 gene who showed ataxia. He began to stagger and slur his words at the age of 48 years. Before that time he had no history of vertigo or episodic ataxia. Subsequently he developed progressive gait disturbance, dysarthria, dysuria, constipation, and impotence. Two years later he was admitted to our hospital. His pulse was 76 and blood pressure 136/86 mmHg. He did not show orthostatic hypotension, and the blood pressure response to standing was normal. Neurological examination revealed slurred speech, moderate ataxia of limbs and trunk, bilateral hyperreflexia in the lower extremities, and bilateral Babinski sign. Muscular strength and sensory modalities were normal. He has no family history of neurological illness. Routine laboratory tests were normal except for hypercholesterolemia and hypertriglyceridemia. Magnetic resonance imaging of the brain showed slight atrophy of the cerebellar vermis and hemispheres and a few lacunar infarcts in the basal ganglia and pons (Fig. 1). We concluded that the ataxia was due to cerebellar degeneration rather than the lacunae in the pons because of the progression of the ataxia and the size of the pontine lesions. Blood samples were obtained from the patient with informed consent. Gene analysis was performed by a modification of the method originally reported [11]. The primers used to amplify the CAG repeat region were: 5′-CAC GTG TCC TAT TCC CCT GTG ATC C–3′ and 5′TGG GTA CCT CCG AGG GCC GCT GGT G–3′. Polymerase chain reaction (PCR) was performed in a total volume of 50 μl, containing 100 ng genomic DNA, 15 pmol each primer, 10 mM Tris-HCl (pH 8.8), 50 mM KCl, 1.5 mM MgCl, 0.1% Triton X–100, 0.2 mM dNTP, and 1.25 U Taq DNA polymerase. The amplification procedure consisted of an initial denaturation at 96°C for 3 min, followed by 35 cycles of denaturation at 96°C for 1 min, annealing at 62°C for 1 min, and extension at 72°C for 1 min in a thermal cycler. The sample was electrophoresed through 4% agarose gel. The sizes of the PCR products were determined by comparing them to a ladder marker. We detected an expanded allele in the SCA6 gene (Fig. 2). To determine the CAG repeat length in the SCA6 gene the PCR products were purified from the gels and sequenced using an automated DNA sequencer (Applied Biosystems, ABI Prism 310 Genetic Analyzer). Direct sequencing revealed 19/7 CAG repeats in the gene. To exclude other forms of hereditary cerebellar ataxia we performed additional gene analysis for SCA1, SCA2, SCA3, SCA7, SCA8, and dentatorubral pallidoluysian atrophy. No abnormally expanded alleles for these genes were detected. Unfortunately, gene analysis could not be performed for his family members. The pathological range of CAG repeats in the SCA6 gene has been reported to be 20 or more [1, 2, 4–10]. In these reports 20 CAG LETTER TO THE EDITORS

A case of spinocerebellar ataxia type 6 mimicking olivopontocerebellar atrophy

Abstract Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant, slowly progressive cerebellar ataxia without multisystem involvement. We report a 57-year-old woman with genetically confirmed SCA6 who showed clinical features of olivopontocerebellar atrophy. Conventional T2-weighted and FLAIR MRI demonstrated high signal in the middle cerebellar peduncles, in addition to mild atrophy of the pons and cerebellum.

Cortical silent period in the tongue induced by transcranial magnetic stimulation

Cortical silent period (SP) of the limb muscles is thought to reflect the cortical excitability. However, the lingual SP has not been examined precisely even in normal subjects. We investigated SP in the tongue induced by transcranial magnetic stimulation (TMS) in 18 controls. Surface electrodes were placed on the lingual dorsum using a bipolar technique. A round coil (13.5 cm in outer diameter) connected with Magstim 200 stimulator was placed on the motor cortex of the tongue, and the intensity of the stimulation was increased stepwise to maximum. SP was detected in all subjects especially at the contralateral side to the stimulated side, without contamination of peripheral SP. The duration of SP depended on the stimulus intensity, while the degrees of muscle contraction did not influence SP. SP of the tongue showed similar characteristics to that of limb muscles. This suggests that SP of lingual muscles can be clinically useful for the evaluation of corticobulbar excitability.

Recurrent Ischemic Stroke in a Patient with the Trousseau Syndrome Treated with Dabigatran

A 70-year-old man with multiple ischemic strokes was diagnosed with cardiac embolism and treated with dabigatran. Three months later, he suddenly developed vertigo and vomiting. Magnetic resonance imaging, showed recurrent lesions and blood tests revealed hypercoagulability, hypoproteinemia, and elevated cytokeratin 19 fragments that serve as a tumor marker of lung cancer. Chest computed tomography showed there were small nodules in bilateral lungs and swollen mediastinal lymph nodes. A conclusive diagnosis was impossible because the patient declined invasive procedures. We suspected primary lung cancer and diagnosed concomitant arterial thrombosis. We initially administered low-molecular-weight heparin, which we later changed to vitamin K antagonist. Although stroke did not recur thereafter, liver metastasis resulted in death 6xa0months later. The effectiveness of novel oral anticoagulants for preventing the Trousseau syndrome remains unclear. Further study is needed to prevent venous and arterial thromboses arising from the Trousseau syndrome.

The Frequency and Risk Factors for Ischemic Stroke in Myotonic Dystrophy Type 1 Patients

INTRODUCTIONnPatients with myotonic dystrophy type 1 have several cardiac abnormalities, especially myocardial conduction disorders. Few studies have investigated cerebral infarction. We investigated the frequency of both symptomatic and asymptomatic ischemic strokes in patients with myotonic dystrophy type 1.nnnMETHODSnPatients who were diagnosed with myotonic dystrophy type 1 using genetic testing or clinical examinations at Asahikawa Medical Center were included. We retrospectively reviewed their medical history, neuroradiological imaging, electrocardiograms, and treatment. Their CHADS2 and CHA2DS2-VASc scores were calculated.nnnRESULTnA total of 108 patients were diagnosed with myotonic dystrophy type 1. Magnetic resonance imaging was performed in 72 and 1 patient whose results were not available was excluded. Among these, 2 patients had atrial flutter and 3 had atrial fibrillation. Regarding the CHADS2 score, 11 patients scored more than 2. Regarding the CHA2DS2-VASc score, 22 patients scored more than 2. Ischemic strokes were found in 9 patients with 1 having an atrial flutter and 4 having atrial fibrillation. All patients with stroke had CHADS2 and CHA2DS2-VASc scores higher than 2. There were significant differences between the 2 groups in atrial fibrillation (Pu2009<u2009.001), CHADS2 score (Pu2009<u2009.001), and CHA2DS2-VASc score (Pu2009<u2009.001).nnnCONCLUSIONSnIschemic stroke in patients with myotonic dystrophy type 1 is associated with atrial fibrillation. The CHADS2 score seems to be useful for the management of patients with myotonic dystrophy type 1. Repeated electrocardiograms are necessary for managing these patients.

Autopsy-proven case of paraneoplastic lower motor neuron disease with sensorimotor neuropathy due to Waldenström's macroglobulinemia: Paraneoplastic motor neuron disease

We report a case of a male patient with a 19‐year history of monoclonal and later polyclonal gammopathy who subsequently developed tetraparesis, bulbar palsy, and respiratory failure. Autopsy findings showed degeneration of the hypoglossal nuclei, prominent neuronal loss and atrophy in the anterior horn of the whole spinal cord despite the presence of mild astrocytosis, degeneration of the gracilis on one side, and infiltration of inflammatory cells, which included B cells and plasma cells in the anterior and posterior roots of the lumbar spinal cord, iliopsoas muscle, and perivascular area of the cervical cord. On immunostaining, cytoplasmic inclusions of phosphorylated transactivation response DNA‐binding protein of 43u2009kDa were observed in the motor neurons and astrocytes of the hypoglossal nuclei and whole spinal cord. The final diagnosis was paraneoplastic lower motor neuron disease with sensorimotor neuropathy due to Waldenströms macroglobulinemia.