[Inherited Creutzfeldt-Jakob disease with four-octapeptide repeat insertional mutation in the prion gene].

We report a case of a 60-year-old man who presented with symptoms of memory loss, gait disorder, and sluggish movement. We considered both Parkinson's disease and multiple system atrophy as possible diagnoses and consequently hospitalized the patient owing to the worsening symptoms and the development of consciousness disorder. During the course of the disease, dementia, loss of consciousness, and movement disorders worsened rapidly within one year after admission, and the patient eventually developed mutism. The significant clinical characteristics of our case included no myoclonus and involuntary tremors in the extremities. There was no periodic synchronous discharge on electro-encephalography and cranial MRI with diffusion-weighted images showed no high-intensity findings in cortex. Prion protein genetic analysis identified four repeated insertional mutations in the octapeptide repeat (OPR) region, and the patient was diagnosed with inherited Creutzfeldt-Jakob disease. Cases of OPR insertional mutations are a few in Japan and occur in about 10% of population in Europe. Creutzfeldt-Jakob disease with OPR insertional mutation shows various clinical manifestations and atypical findings on electroencephalography and cranial MRI. Diagnosing for Creutzfeldt-Jakob disease with OPR insertional mutation is important in Prion protein genetic analysis.

[Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS): a case report].

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a rare form of multisystem ataxia defined by a triad of cerebellar impairment, bilateral vestibular hypofunction, and somatosensory deficit. Here we present a patient with CANVAS. A 76-year-old woman whose parents were cousins had noted slowly worsening gait imbalance since age 67. Peripheral sensory impairment was evident since age 73. When examined at 74, she had a frequent cough. The neurologic examinations showed scanning speech, downbeat nystagmus, pursuit eye movements with saccadic features, truncal ataxia, and mild dysmetria of the extremities. The Romberg test was positive. Light touch, pinprick, and vibration sensation were absent in the distal lower limbs, where allodynia could be demonstrated. Ankle jerk reflex was diminished. Muscle strength was normal. Nerve conduction studies disclosed absence of sensory nerve action potentials in all limbs, while motor conduction was normal except for decreased amplitude of left median and bilateral ulnar nerve compound motor action potentials. MRI of the brain demonstrated cerebellar atrophy. The eye tracking test for the smooth pursuit and visually enhanced vestibulo-ocular reflex test demonstrated functional impairments. Both the bithermal caloric test and the video head impulse testing showed sever hypofunction of the bilateral semicircular canal. In sum, somatosensory deficit and otoneurologic examinations indicated bilateral vestibulopathy which, together with the patient's and cerebellar impairment, confirmed the diagnosis of CANVAS.

The characteristics of camptocormia in patients with Parkinson's disease: A large cross-sectional multicenter study in Japan.

PURPOSE: The goal of the present study was to clarify the clinical characteristics and laboratory results of parkinsonian symptoms among patients with and without camptocormia. METHODS: Seventy-eight Parkinson's disease (PD) patients with camptocormia and 78 PD patients without camptocormia underwent a neurological examination, a blood test, and spinal magnetic resonance imaging (MRI). PD with camptocormia group and PD with non-camptocormia group were matched on age, age at PD onset, and sex. PRINCIPAL RESULTS: Camptocormia group had significantly higher prevalence of compression fractures, more severe parkinsonian symptoms, and a greater incidence of dementia than those without camptocormia. Serum creatine kinase levels in camptocormia group significantly elevated compared with non-camptocormia group. There were higher prevalence of abnormal findings in spine MRI including compression fractures and paravertebral muscle changes in camptocormia group compared with non-camptocormia group. MAJOR CONCLUSIONS: Camptocormia is associated with a greater prevalence of compression fractures and associated with greater UPDRS part II, part III score, axial score, and lower MMSE in this cross-sectional study. Thus, it can be concluded that camptocormia in PD is predominantly myopathic.

[A case of neuromyelitis optica associated with anti-aquaporin 4 antibody and other autoantibodies].

We report a patient with optic neuropathy and longitudinally extensive myelitis associated with anti-aquaporin 4 (AQP4) antibody and other autoantibodies. An 89-year-old woman presented with progressive numbness and weakness of the extremities which had acutely developed. She also complained of neck pain and gait disturbance. The results of a general physical examination were unremarkable. Neurologic examination disclosed right optic atrophy, an absence of touch sensation, pain, and muscular weakness in all her extremities. Her deep tendon reflexes were decreased, and the Babinski sign was bilaterally positive. Immunoserologic study yielded positive titers for anti-nuclear antibody (ANA), anti-double-stranded DNA, anti-Sjögren syndrome (SS)-A, anti-SS-B, and anti-ribonucleoprotein (RNP) antibodies. A lumbar cerebrospinal fluid examination showed a protein concentration of 54 mg/dL, a glucose concentration of 50 mg/dL (simultaneous blood concentration, 140 mg/dL), and a cell count of 2/mm(3). Chest radiography revealed interstitial pneumonia. Magnetic resonance imaging (MRI) of the cervical spine showed spondylotic cervical canal stenosis with cord impingement. T2-weighted MR images demonstrated increased signal intensity extending from C2 to C6, while contrast enhancement was noted in T1-weighted MR images upon gadolinium-DTPA administration. We suspected longitudinally extensive myelitis associated with the autoimmune disorders systemic lupus erythematosus and Sjögren syndrome. After intravenous methylprednisolone administration, her neurologic abnormalities gradually decreased, while MRI no longer showed increased signal or contrast enhancement. Anti-AQP4 antibody titers were positive. We consider that this patient had a neuromyelitis optica (NMO) spectrum disorder which was associated with systemic autoimmune disease. The possibility of NMO should be considered in similar patients with autoimmune disease, and anti-AQP4 antibody should be assessed.

[Autopsy case of dural thickening caused by widespread dural vein thrombosis associated with disseminated bone marrow carcinomatosis].

A 64-year-old woman was referred to our hospital because of disturbance of consciousness. She had undergone distal gastrectomy for gastric carcinoma 17 years previously. General physical examination was unremarkable, neurologic examination disclosed hyperactive deep tendon reflexes in the upper limbs. Laboratory abnormalities included elevations of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), and findings suggesting disseminated intravascular coagulation (DIC). Lumbar cerebrospinal fluid showed a protein concentration of 408 mg/dl and a glucose concentration of 82 mg/dl (blood: 110 mg/dl), as well as a cell count of 16/mm3. Cranial computed tomography indicated brain edema. Magnetic resonance imaging (MRI) of the brain showed diffuse thickening of the dura mater, with contrast enhancement upon gadolinium-DTPA administration. These findings suggested hypertrophic pachymeningitis. Magnetic resonance venography (MRV) showed occlusion of the left transverse sinus and attenuation of the straight sinus. MRI of the spine as well as gallium scintigrams demonstrated multiple areas of increased uptake in areas near the skull and spine. We therefore suspected tumor metastasis. The patient was given heparin as well as pulse therapy with methylprednisolone, but she died 7 weeks after symptom onset. At postmortem examination, the dura was thickened. Histopathologically, numerous tumor cell emboli in the dura were confined to the lumens of veins. The tumor cells were thought to have metastasized to the dura through the vertebral venous plexus (Batson's plexus). Immunostaining demonstrated immunoreactivity of tumor cells to epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA). The primary origin of the carcinoma was not precisely identified by these findings. Widespread dural vein tumor emboli should be taken into consideration as a cause in cases that develop rapid deterioration of consciousness associated dura mater thickening.

Measurement of low-frequency ultrasonic wave in water using an acoustic fiber sensor.

An acoustic fiber sensor for measurement of ultrasonic waves, which used the approximate Raman-Nath diffraction effect where light diffraction waves were generated in an optical fiber by strain due to the ultrasonic waves, was proposed and examined. In order to characterize the acoustic fiber sensor as a basic study, measurements of low-frequency ultrasonic waves in water were examined using a step index fiber operating as a detection sensor. The results showed that characteristics of detected signals agreed with the theoretical prediction based on Fraunhofer diffraction. This indicates that our proposed fiber sensor can be used for the detection of low-frequency ultrasonic waves as well as the transmission of light diffraction signals.

Mechanism of action of voltage-gated K+ channel antibodies in acquired neuromyotonia.

Acquired neuromyotonia (ANM) is associated with antibodies to voltage-gated K+ channels (VGKCs). ANM sera reduce the number of K+ currents in neuronal cell lines, but it is not clear how the antibodies act. Here, we show by using the NB-1 cell line that the reduction in K+ currents by IgG is independent of added complement. IgG Fc and Fab fragments from ANM sera had no effect, but three of four ANM F(ab')2 fragments significantly reduced K+ currents. Thus, cross-linking of the channels by divalent antibodies is likely to be an important mechanism in reducing K+ currents.

[A patient with von Recklinghausen's disease associated with polymyositis, asymptomatic pheochromocytoma, and primary hepatic leiomyosarcoma].

A 72-year-old woman with von Recklinghausen's disease was referred to our hospital because of pain and muscle weakness in her thighs. She had elevated serum values of creatine kinase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and aldolase. Based on these results, a diagnosis of polymyositis was made. Treatment with prednisolone improved muscle strength, and laboratory values returned to normal. Computed tomography, magnetic resonance imaging of the abdomen, and 131I-metaiodobenzyl guanidine MIBG scintigraphy demonstrated a tumor 3 cm in diameter in the region of the left adrenal gland. Endocrinologic investigation disclosed elevation of serum and urine catecholamines. Since the blood pressure was normal, nonfunctioning pheochromocytoma was diagnosed clinically. The nonhypertensive course was attributed to reduced vascular response to noradrenaline. Serum lactate dehydrogenase. alkaline phosphatase. and asparate aminotransferase became elevated, and abdominal computed tomography showed a well-defined mass measuring 13 x 12 x 10 cm in the right lobe of the liver. The patient underwent right trisegmentectomy and left adrenalectomy. Histologically the adrenal tumor was a typical pheochromocytoma. The hepatic tumor was a leiomyosarcoma consisting of elongated spindle-shaped atypical cells arranged in intersecting bundles. Immunohistochemically, the cells of this tumor were reactive for alpha-smooth muscle actin and vimentin. The leiomyosarcoma recurred and metastasized to the liver. Eight months after onset of symptom, the patient developed hepatic coma and died. The mean age at presentation with pheochromocytoma in von Recklinghausen's disease patients age is 42 years. Our patient was considerably older. To the best of our knowledge this is the first report of a patient with von Recklinghausen's disease developing polymyositis. asymptomatic pheochromocytoma, and primary hepatic leiomyosarcoma and illustrates the need to remain aware of the possibility of cancer in von Recklinghausen's disease.

Isaacs' syndrome as a potassium channelopathy of the nerve.

Isaacs' syndrome (acquired neuromyotonia) is an antibody-mediated potassium channel disorder (channelopathy). The target channel proteins of the antigens are voltage-gated potassium channels (VGKCs), especially dendrotoxin-sensitive fast potassium channels. The suppression of voltage-gated outward K(+) current by antibodies induces hyperexcitability of the peripheral nerve. Patch clamp studies show that antibodies may not directly block the kinetics of VGKCs but may decrease channel density. Electrophysiological, pharmacological, and immunological findings indicate that the site of origin of spontaneous discharges is principally in the distal portion of the motor nerve and/or within the terminal arborization. The spectrum of potassium channelopathies is expanding. The existence of antibodies against VGKCs should be considered in patients who present with generalized nerve hyperexcitability of undetermined etiology.

Reflejo orbicular de los párpados en la paraparesia espástica tropical y otras enfermedades neurológicas

El reflejo orbicular de los ojos (ROO) obtenido por estimulación eléctrica produce usualmente dos respuestas (R1 y R2); sin embargo, unas poco comunes como la "respuesta temprana contralateral" (R1K), o el registro de dos o más componentes en la respuesta intermedia (R2) son más importantes de lo que hasta ahora se había creído. Estos "raros" hallazgos han sido apreciados en entidades que afectan el sistema nervioso periférico como la parálisis facial y el sistema nervioso central como la enfermedad de Parkinson (EP), varias clases de distonías y la paraparesia espástica tropical/mielopatía asociada al HTLV-I(HAM/TSP). Dichos registros poco comunes se han descrito en la esclerosis lateral amiotrófica (ELA) o la esclerosis múltiple (EM). Trastornos de la regeneración axonal, secundarios a un daño nervioso periférico y/o fallas en la inhibición interneuronal mediada por la corteza cerebra, el tracto piramidal o los ganglios basales (GB), parecen ser los mecanismos más importantes de estas respuestas principalmente a nivel patológico. De otro lado, la respuesta tardía (R3) del ROO, descrita más recientemente, viaja por rutas nerviosas diferentes a las conocidas para las dos primeras respuestas (R1, R1K y R2) y se considera esencialmente nociceptiva. Esta respuesta es modulada a nivel de tallo cerebral, y muy probablemente, regulada por la corteza cerebral, y además, parece ser importante en el estudio fisiopatológico de las vías relacionadas con el dolor en el ser humano. Las diferencias del ROO entre la HAM/TSP y la esclerosis múltiple (EM) podrían ser útiles para comprender los mecanismos de la espasticidad en éstas y otras entidades relacionadas en futuros estudios clínicos y neurofisiológicos.