A case of GNE myopathy mimicking hereditary motor neuropathy.

A 36-year-old woman who presented with upper limb distal weakness since the age of 15 years, with gradual progression to the lower limbs, is reported. Hereditary motor neuropathy was initially suspected based on distal weakness and hyporeflexia; however, whole exome sequencing accidentally revealed a compound heterozygous variant in the GNE gene, and ultrasound revealed increased homogeneous echogenicity in the involved muscles, which is characteristic of myopathic changes. Muscle magnetic resonance imaging revealed fatty infiltration in all limb muscles, sparing the triceps brachii, vastus lateralis and vastus medialis. Muscle biopsy revealed intracytoplasmic rimmed vacuole, supporting the diagnosis of GNE myopathy.

Image multiplexing and encryption using the nonnegative matrix factorization method adopting digital holography.

In this paper, a joint multiple-image encryption and multiplexing system, which utilizes both the nonnegative matrix factorization (NMF) scheme and digital holography, is proposed. A number of images are transformed into noise-like digital holograms, which are then decomposed into a defined number of basis images and a corresponding weighting matrix using the NMF scheme. The determined basis images are similar to the digital holograms and appear as noise-like patterns, which are then stored as encrypted data and serve as the lock in an encryption system. On the other hand, the column vectors in the weighting matrix serve as the keys for the corresponding plain images or the addresses of the multiplexed images. Both the increased uniformity of the column weighting factors and the parameters used in the digital holography enhance the security of the distributed keys. The experimental results show that the proposed method can successfully perform multiple-image encryption with high-level security.

A novel DNAJB6 mutation causes dominantly inherited distal-onset myopathy and compromises DNAJB6 function.

BACKGROUND: Mutations in the DNAJB6 gene have been identified as a rare cause of dominantly inherited limb-girdle muscular dystrophy or distal-onset myopathy. MATERIALS AND METHODS: Exome sequencing was performed to investigate a Taiwanese family with a dominantly inherited distal-onset myopathy. Functional effects of the causal mutation were investigated in vitro. RESULTS: Exome sequencing of the two affected individuals in this family identified a heterozygous mutation, c.287C>T (p.Pro96Leu) in the DNAJB6 gene, which co-segregated with the myopathy within all 12 family members. Notably, this mutation is novel and localizes within the glycine and phenylalanine-rich (G/F) domain and alters an amino acid residue previously reported with a different mutation. Furthermore, immunofluorescence analyses and filter trap assay demonstrated that the c.287C>T (p.Pro96Leu) mutation possessed a dominant negative effect on the anti-aggregation function of DNAJB6 protein. CONCLUSION: This study expands the molecular spectrum of DNAJB6 mutations and also emphasizes the pathogenic role of DNAJB6 dysfunction in distal-onset myopathy.

Acute increase of complexity in the neurocardiovascular dynamics following carotid stenting.

OBJECTIVE: Percutaneous carotid angioplasty and stenting (CAS) has been used to improve cerebral circulation and autoregulation. However, whether CAS ameliorates the autonomic regulatory dynamics remains unclear. This prospective study examines the neurocardiovascular dynamics following carotid stenting. METHODS: Thirty minutes electrocardiograms were recorded at three different time points (pre-operative, 1-h post-operative, 1-day post-operative) on twelve male patients (mean age 70.8 ± 9.6 years) receiving unilateral primary CAS. The HR data were analyzed by the conventional heart rate variability (HRV) and the multiscale entropy (MSE) methods; the former associates with autonomic activities and the latter quantifies the regulatory complexity of heart beat intervals. Loss of complexity at multiple scales has been associated with decoupled regulatory network in vivo. RESULTS: Conventional HRV indices showed no difference after CAS. Complexity indices increased significantly on scales 2-8 at 1-h and on scales 2-3 1-day post-treatment. The lower scale MSE (1-5) correlated with the frequency components of conventional HRV indices. The increased complexity could imply a restoration of the neurocardiovascular dynamics on the path to a healthier state. CONCLUSIONS: Primary CAS can induce a recovery in the neurocardiovascular regulatory dynamics in patients with high-grade carotid stenosis.

Microscopic polyangiitis presenting with capsular warning syndrome and subsequent stroke.

A 55-year-old man developed ischemic stroke after three episodes of transient dysarthria and left hemiplegia, a typical manifestation of capsular warning syndrome. Magnetic resonance imaging of the brain showed bilateral basal ganglionic infarction. The patient had no significant risk of stroke. However, the systemic manifestations, an elevated titer of perinuclear anti-neutrophilic cytoplasmic antibody and a skin biopsy revealing leukocytoclastic venulitis confirmed the undrlying microscopic polyangiitis.

MPZ mutation G123S characterization: evidence for a complex pathogenesis in CMT disease.

OBJECTIVES: To characterize the clinical and cellular phenotypes of a novel MPZ mutation identified in a Chinese family with Charcot-Marie-Tooth (CMT) disease type 1B. METHODS: The family was evaluated clinically, electrophysiologically, pathologically, and genetically. The wild-type and mutant P(0) fused with fluorescent proteins were expressed in vitro to monitor their intracellular trafficking. Adhesion assay was also performed to evaluate the adhesiveness of cells. RESULTS: The novel MPZ mutation, c.367G>A, is associated with a late-onset demyelinating CMT phenotype with autosomal dominant inheritance. The median motor nerve conduction velocities of patients in this family ranged from 15.7 to 19.6 m/second. The neuropathologic studies from a sural nerve biopsy revealed a severe loss of myelinated fibers, and some onion bulb formation with clusters of regenerative fibers. Fluorescence analysis demonstrated that the mutant protein was retained ectopically in the endoplasmic reticulum and Golgi apparatus. Adhesion assay demonstrated a defective adhesiveness of cells expressing the mutant P(0)G123S protein. CONCLUSION: The novel P(0)G123S mutation is associated with typical findings of late-onset demyelinating polyneuropathy in the electrophysiologic and pathologic studies, putatively resulting from aberrant intracellular trafficking of the mutant P(0) protein, which compromises the adhesiveness of the cells.

Mononeuropathy multiplex and chylothorax as earlier manifestations of pulmonary tuberculosis.

Mononeuropathy multiplex (MNM) and chylothorax are rare clinical disorders. The concurrence of these two disorders with Mycobacterium tuberculosis infection has not been reported. We herein report a patient who was initially diagnosed with fever of unknown origin and MNM, and then developed chylothorax. Pulmonary tuberculosis was proved 1 month after chylothorax appeared. With low-dose prednisolone 15 mg day(-1) and anti-tuberculosis drugs, all these disorders completely resolved 1 year later.

Brain dysfunction explored by long latency reflex: a study of adrenomyeloneuropathy.

OBJECTIVES: We can assess brain function by measuring the cortical relay time (CRT) of long latency reflex (LLR) of hand muscle. We would study if measurement of CRT of LLR can explore the brain involvement of adrenomyeloneuropathy (AMN). METHODS: Two AMN patients were included in the study. Both of them had spastic gait and mild sensory deficits but normal mental function. The LLRs were provoked at the first dorsal interosseous muscle by electrical stimulation of the middle finger. We measured the latency of LLR and its CRT. RESULTS: Delayed LLR and prolonged CRT were noted in AMN patients, even though the magnetic resonance imaging of brain did not show any significant abnormalities. CONCLUSIONS: Measuring CRT of LLR reveals brain involvement of AMN patients, and it is an adjunct in the assessment of brain function though without specific anatomic diagnosis.

Problem-based, small-group tutorial learning in clinical neurology for second-year medical students.

BACKGROUND: Problem-based learning (PBL) in small-group tutorials has been a trend in medical education. Chinese students are known to be reserved and passive; thus, they may not be adaptable to PBL. Neuroanatomy, important to clinical neurology, is difficult to learn. We incorporated clinical neurology with PBL, complementary to the traditional neuroanatomy curriculum, to evaluate the feasibility of PBL for Chinese students in Taiwan. METHODS: Forty-two second-year medical students and seven tutors participated in the clinical neurology PBL small-group tutorials. Twelve case reports were discussed weekly beginning in February, 1999. Each case was designed to meet the progressive curriculum of the neuroanatomy course. The tutors evaluated the students by the degree of their preparation, participation, key-point comprehension and interaction. All tutors and students filled out questionnaires at the end of each session. RESULTS: The majority of the students and tutors agreed that the case materials were clearly written. Ninety percent of the students agreed that the case materials matched the traditional content of neuroanatomy. Eighty-five percent of students and 71% of tutors were satisfied and found the class rewarding. Ninety-one percent of students and 74% of tutors were in favor of PBL being continued. CONCLUSIONS: This preliminary PBL, small-group tutorial learning in clinical neurology showed satisfactory results and was, indeed, complementary to a traditional neuroanatomy course. The students, as early as during the second year of their medical school education, were able to learn through the PBL. More integration of basic and clinical sciences by PBL may be considered in future curricula designs.

Automatic breast region extraction from digital mammograms for PACS and telemammography applications.

High spatial resolution results in very large digital mammogram file sizes. For telemammography, and picture archiving and communication systems, the large file issue introduces technical difficulties in image transmission, storage, and display. We propose extracting the breast region from the mammogram to reduce the image file size. The challenge is on how to faithfully extract breast regions from digital mammograms generated from different types of acquisition systems that contain various imaged compositions. We report an algorithm to automatically identify the orientation of breast region and extract the breast region from mammograms. Breast regions extracted from full-field digital mammograms reduce file sizes by three to five folds.

Measurement of the urinary lactate:creatinine ratio for the early identification of newborn infants at risk for hypoxic-ischemic encephalopathy.

BACKGROUND: Newborn infants with perinatal asphyxia are prone to the development of hypoxic-ischemic encephalopathy. There are no reliable methods for identifying infants at risk for this disorder. METHODS: We measured the ratio of lactate to creatinine in urine by proton nuclear magnetic resonance spectroscopy within 6 hours and again 48 to 72 hours after birth in 58 normal infants and 40 infants with asphyxia. The results were correlated with the subsequent presence or absence of hypoxic-ischemic encephalopathy. RESULTS: Hypoxic-ischemic encephalopathy did not develop in any of the normal newborns but did develop in 16 of the 40 newborns with asphyxia. Within six hours after birth, the mean (+/-SD) ratio of urinary lactate to creatinine was 16.75+/-27.38 in the infants who subsequently had hypoxic-ischemic encephalopathy, as compared with 0.09+/-0.02 in the normal infants (P<0.001) and 0.19+/-0.12 in the infants with asphyxia in whom hypoxic-ischemic encephalopathy did not develop (P<0.001). A ratio of 0.64 or higher within six hours after birth had a sensitivity of 94 percent and a specificity of 100 percent for predicting the development of hypoxic-ischemic encephalopathy. The sensitivity and specificity of measurements obtained 48 to 72 hours after birth were much lower. The mean ratio of urinary lactate to creatinine was significantly higher in the infants who had adverse outcomes at one year (25.36+/-32.02) than in the infants with favorable outcomes (0.63+/-1.50) (P<0.001). CONCLUSIONS: Measurement of the urinary lactate: creatinine ratio soon after birth may help identify infants at high risk for hypoxic-ischemic encephalopathy.

Botulism: heart rate variation, sympathetic skin responses, and plasma norepinephrine.

BACKGROUND: Botulism may involve the autonomic nervous system. METHODS: We assessed the autonomic function of 6 botulism patients with heart rate variations, sympathetic skin responses, and plasma norepinephrine. RESULTS: Two weeks after onset, all the patients had absent sympathetic skin response in the palm and sole. Compared with controls, the heart rate variation of botulism patients was significantly decreased at rest (3.1 +/- 1.2% vs. 20.9 +/- 2.0%, p = 0.0018) and during deep breathing (4.3 +/- 2.3% vs. 29.7 +/- 2.6%, p = 0.0018). The botulism patients had significantly lower plasma norepinephrine levels (supine 29.2 +/- 10.1 pg/ml vs. 257.5 +/- 65.8 pg/ml, p = 0.0018; standing 40.3 +/- 13.1 pg/ml vs. 498.5 +/- 85.6 pg/ml, p = 0.0018). The heart rate variation and sympathetic skin response was greatly improved 6 months after onset. CONCLUSIONS: Heart rate variation, absence of sympathetic skin response, and low plasma norepinephrine are all manifestations of autonomic dysfunction in botulism patients.

Use of botulinum toxin A in the treatment of hemifacial spasm and blepharospasm.

BACKGROUND: Hemifacial spasm and blepharospasm are both dystonic disorders. They may seriously affect individuals' lifestyle and social activities. In 1990, the Food and Drug Administration of the USA approved botulinum toxin A as a therapeutic agent in the treatment of hemifacial spasm and blepharospasm. We present a therapeutic review of botulinum toxin A in 80 patients in Taiwan. METHODS: Fifty-eight patients with hemifacial spasm and 22 with blepharospasm. Botulinum toxin A was prepared and injected into the facial and eyelid muscles. Patients were monitored every two weeks and classified into four groups (excellent, moderate, mild and no improvement) according to the clinical improvement scale. Complications were also recorded. RESULTS: A total of 86.2% of hemifacial spasm patients and 81.8% of blepharospasm patients had excellent improvement on the spasm intensity scale, while 6.8% of hemifacial spasm and 9.0% of blepharospasm patients had moderate improvement. The complication rate was low and included transient mild facial weakness (5%), ptosis (3.8%), eyelid swelling and/or ecchymosis (3.8%), nausea/vomiting (2.5%) and transient severe facial weakness (1.3%). CONCLUSION: Botulinum toxin A is an excellent therapeutic agent to improve spasm intensity and has a low complication rate.

Heterogeneity of antibody specificity in Taiwanese patients with polyneuropathy and IgM paraproteinemia.

About half of the Caucasian patients with chronic polyneuropathy and IgM paraproteinemia show serum anti-myelin-associated glycoprotein (MAG) and anti-sulfoglucuronosyl glycosphingolipid (SGGLs) activities. These antibody activities have been demonstrated to react with a carbohydrate epitope known as the HNK-1 or sulfoglucuronic acid (SGA) epitope. However, in Asian populations the occurrence of serum anti-SGA activities has been reported to be relatively rare. We investigated 5 cases of chronic polyneuropathy with IgM paraproteinemia from Taiwan and found that 3 of them had high-titer serum anti-SGA (SGGL/MAG) antibody activities. The clinical symptoms of these 3 patients were consistent with sensory dominant polyneuropathy with a severer involvement of the lower limbs than of the upper limbs. Electromyography and nerve conduction studies revealed severe sensory nerve involvement (no response in 3 cases) and moderate slowing of motor conduction velocity (MCV) without conduction block. The decrease in MCV correlated well with anti-SGA antibody titer (less than 30 m/s with the titration of 1:12, 800, normal 55-60 m/s). Pathological findings showed active demyelinating polyneuropathy with myelin ovoid and myelinated fiber loss. Our data suggest that anti-SGGL antibody activities may not be very rare among Asian populations. Additionally, there seems an intriguing possibility that the titer of this antibody correlates with the severity of peripheral nerve involvement in patients of demyelinating polyneuropathy with IgM paraproteinemia.

Estimation of myocardial glucose utilisation with PET using the left ventricular time-activity curve as a non-invasive input function.

The validation study is described of a new modelling method that has been developed, using tracer kinetic modelling with positron emission tomography (PET) to achieve non-invasive measurement of myocardial metabolic rate of glucose (MMRGlc). Eight data sets obtained from dynamic cardiac PET 2-[18F]fluoro-2-deoxy-D-glucose (FDG) studies on human subjects are employed, and the estimation of MMRGlc using both the new and traditional methods is compared. The results from all eight human FDG studies are consistent with those from previous computer simulations. With the new method, the estimated mean of K (a parameter directly proportional to MMRGlc) increases by about 8%, and that of k 4 (the rate constant of FDG dephosphorylation) decreases by about 48%. The approach should be more suitable for use in dynamic cardiac PET studies when non-invasive means are used to obtain the plasma time-activity curve from left-ventricle PET images.

An electrophysiologic and pathologic study of peripheral nerves in individuals with Machado-Joseph disease.

BACKGROUND: Machado-Joseph disease (MJD) is characterized by cerebellar ataxia, pyramidal signs, progressive external ophthalmoplegia, and variable degrees of bulging eyes and dystonia. Electrophysiologic and histologic alterations of the peripheral nervous system in patients with MJD have rarely been reported. METHODS: The peripheral nerves of four patients with MJD who were identified by polymerase chain reaction were subjected to electrophysiologic testing and histologic study. Correlation analyses were made between clinical parameters and the electrophysiologic as well as histologic changes. RESULTS: Electrophysiologic studies demonstrated a marked reduction of sensory action potential, as well as a decrease in the compound motor action potential. Light microscopy of the sural nerves revealed marked loss of myelinated fibers, and morphometry studies showed a loss of large myelinated fibers. The severity of these pathologic changes was not related to the duration of the disease. CONCLUSIONS: In MJD, the peripheral nervous system was frequently affected. These findings were similar to those seen in Friedreich's ataxia, suggesting a loss of sensory and motor fibers probably following a lesion of the dorsal root ganglion and the anterior horns in the spinal cord.