Tomoo Inukai

Tumor necrosis factor-alpha and its receptors contribute to apoptosis of oligodendrocytes in the spinal cord of spinal hyperostotic mouse (twy/twy) sustaining chronic mechanical compression.

Study Design. To examine the distribution of apoptotic cells and expression of tumor necrosis factor (TNF)-α and its receptors in the spinal hyperostotic mouse (twy/twy) with chronic cord compression using immunohistochemical methods. Objective. To study the mechanisms of apoptosis, particularly in oligodendrocytes, which could contribute to degenerative change and demyelination in chronic mechanical cord compression. Summary of Background Data. TNF-α acts as an external signal initiating apoptosis in neurons and oligodendrocytes after spinal cord injury. Chronic spinal cord compression caused neuronal loss, myelin destruction, and axonal degeneration. However, the biologic mechanisms of apoptosis in chronically compressed spinal cord remain unclear. Methods. The cervical spinal cord of 34 twy mice aged 20 to 24 weeks and 11 control animals were examined. The apoptotic cells were detected by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) staining. The expression and the localization of TNF-α, TNF receptor 1 (TNFR1), and TNF receptor 2 (TNFR2) were examined using immunoblot and immnohistochemical analysis. Results. The number of TUNEL-positive cells in the white matter increased with the severity of compression, which was further increased bilaterally in the white matter of twy/twy mice. Double immunofluorescence staining showed that the number of cells positive for TUNEL and RIP, a marker of oligodendrocytes, increased in the white matter with increased severity of cord compression. Immunoblot analysis demonstrated overexpression of TNF-α, TNFR1, and TNFR2 in severe compression. The expression of TNF-α appeared in local cells including microglia while that of TNFR1 and TNFR2 was noted in apoptotic oligodendrocytes. Conclusion. Our results suggested that the proportion of apoptotic oligodendrocytes, causing spongy axonal degeneration and demyelination, correlated with the magnitude of cord compression and that overexpression of TNF-α, TNFR1, and TNFR2 seems to participate in apoptosis of such cells in the chronically compressed spinal cord.

Adenovirus‐mediated retrograde transfer of neurotrophin‐3 gene enhances survival of anterior horn neurons of twy/twy mice with chronic mechanical compression of the spinal cord

Chronic mechanical compression of the spinal cord causes neural tissue damage, including loss of anterior horn cells around the level of injury. Exogenous delivery of neurotrophins to neuronal cells could provide neuroprotection to a spinal cord subjected to mechanical injury. We investigated the efficacy of retrograde gene delivery of adenoviral vector (AdV) carrying neurotrophin‐3 (NT‐3) gene into twy (twy/twy) mouse spinal cord anterior horn neurons with chronic and progressive mechanical compression at C1‐C2 level. AdV‐NT‐3 was used for retrograde delivery via the sternomastoid muscle to the cervical spinal accessory motoneurons in 16‐week‐old adult twy mice with relatively mild spinal cord compression. Four weeks after the AdV‐NT‐3 or AdV‐β‐galactosidase cDNA (LacZ) as a marker gene injection, the compressed cervical spinal cord was examined histologically, immunohistologically, and by immunoblot analysis. Immunoreactivity to NT‐3 was significantly enhanced in the AdV‐NT‐3‐injected twy mice compared with the AdV‐LacZ‐injected mice. The numbers of anterior horn neurons of Nissl‐, choline acetyltransferase (ChAT)‐, and trkC‐stained and wheat germ agglutinin‐horseradish peroxidase (WGA‐HRP)‐labeled neurons at the spinal cord level with maximum compression were significantly higher in AdV‐NT‐3‐transfected than in AdV‐LacZ‐transfected twy mice. Retrograde NT‐3 gene transfer to twy mouse anterior horn neurons increased neurite axonal length and arborization of WGA‐HRP‐labeled neurons. Our results suggest that targeted retrograde NT‐3 gene delivery is feasible in the intact animal and that it enhances neuronal survival even under chronic mechanical compression of the spinal cord.

Visualization of intraneural edema using gadolinium-enhanced magnetic resonance imaging of carpal tunnel syndrome

BackgroundIn general, carpal tunnel syndrome (CTS) is diagnosed based mainly on clinical findings and electrophysiology. However, the pathological state of the compressed median nerve could not be shown on imaging. Gadoliniumenhanced magnetic resonance (MR) imaging may give us an idea about the status of the blood-nerve barrier of peripheral nerves. Therefore, detecting intraneural edema may be a way of diagnosing entrapment neuropathy. The present study investigated the diagnostic role of gadolinium-enhanced MR imaging of CTS.MethodsThe subjects were 23 patients (34 hands) with idiopathic CTS. To serve as control subjects, 12 wrists of asymptomatic volunteers were studied. Using the spin-echo method, T1- and T2-weighted axial MR images were obtained. Intravenously injected gadolinium was used to obtain enhanced images. We studied the relation between nerve enhancement and the symptomatology.ResultsAfter intravenous injection of gadolinium, there was no enhancement of the unaffected nerves in the carpal tunnels of the control group. Gadolinium enhancement was found in only 87% of patients with CTS who visited the hospital at an early stage and therefore had no nerve deficiency on electrophysiological studies (39%). Based on this finding, during the early stages when the nerve is in a state of neuropraxia, gadolinium-enhanced MR imaging of the median nerve might prove to be the most sensitive modality for detecting early nerve dysfunction. MR imaging also revealed a higher frequency of enhancement in the advanced stage of CTS with muscle atrophy.ConclusionsWe conclude that gadolinium-enhanced MR imaging can detect not only morphological changes but also pathological changes of the median nerve in patients with CTS. Currently, gadolinium-enhanced-MR imaging is probably most commonly used to image patients who have ambiguous electrodiagnostic studies and clinical examination in an early stage of CTS.

Target muscles for retrograde gene delivery to specific spinal cord segments

Targeted retrograde gene delivery into the injured spinal cord is less invasive for the damaged tissue. One of the advantages of this approach is the possible selection of target organs according to the level of spinal cord injury. We evaluated nine candidate target organs for retrograde delivery of an adenovirus vector carrying beta-galactosidase (AdV-LacZ) gene to cervical, thoracic and lumbar spinal cord segments. One week after vector injection into each muscle, we assessed the LacZ gene expression in the spinal cord by X-gal staining. The most appropriate target organs with high transduction efficacy were the sternomastoid and clavotrapezius muscles for cervical spinal cord, tibialis anterior and the gastrocnemius muscles for the lumbar spinal cord. Retrograde gene delivery to the thoracic spinal cord was inefficient probably due to the small number of anterior horn neurons in the region. Gene expression was mainly identified over the anatomical area of innervation and not into other body organs. Our results suggested that retrograde delivery of adenovirus genome to the cervical and lumbar spinal cord segments seems feasible by injection of an adenoviral vector into the appropriate target organ. Adenovirus vector is an efficient retrograde tracer since it can deliver the carried gene to a wide area of the spinal cord and not to other body organs.

Cervical angina: a seemingly still neglected symptom of cervical spine disorder?

Study Design:Retrospective, case series.Design:A review of 10 surgical cases with symptoms of cervical angina.Objective:To stress the importance of symptoms of cervical angina in patients with cervical spine disorders.Setting:Fukui University Hospital, Japan.Results:A total of 10 patients complaining of symptoms of cervical angina were admitted with a tentative diagnosis of coronary artery disease. Pain relief was achieved by anterior surgical decompression in all patients.Conclusion:We stress that physicians should be aware of the symptoms of cervical angina and that surgical intervention often leads to complete relief of symptoms.

Second lumbrical-interossei nerve test predicts clinical severity and surgical outcome of carpal tunnel syndrome

The purpose of this study was to examine the utility of the second lumbrical-interossei nerve (2L-IN) test in the diagnosis of carpal tunnel syndrome (CTS). We examined 65 patients with suspected unilateral CTS using the 2L-IN test, in addition to the standard electrophysiological test. The operative cases were divided into three classes of severity based on Paduas neurophysiological classification: extreme CTS (absence of median motor and sensory response); severe CTS (absence of sensory response, abnormal distal motor latency [DML]); and moderate CTS (abnormal sensory nerve conduction velocity, abnormal DML). With the 2L-IN test, the extreme CTS group could be further subdivided into extreme CTS-A (both abductor pollicis brevis [APB]- compound muscle action potential [CMAP] and 2L-CMAP not recordable) and extreme CTS-B (2L-CMAP recordable, APB-CMAP not recordable). Patients with extreme CTS and severe CTS were older, had chronic symptoms, and poorer outcome compared with the moderate CTS patients. Patients of the moderate CTS group were almost all satisfied with the results of surgery. The electrodiagnostic severity correlated with the clinical outcome. Severe strangulation of the thenar muscle branch was identified in patients in the extreme CTS-B group, requiring decompression of the thenar muscle branch rather than conventional simple transverse ligament detachment.

Additional method for diagnosis of carpal tunnel syndrome: value of the second lumbrical-interossei test (2L-INT).

We examined 57 hands referred with suspected carpal tunnel syndrome (CTS) using the second lumbrical-interossei nerve test (2L-INT) as well as standard test. Sensory nerve conduction velocity (SCV) was detectible in 67% of patients (38/57), the abductor pollicis brevis-compound muscle action potential (APB-CMAP) in 84% (48/57), 2L-CMAP in 96% (55/57) and the first interossei palmares muscle (INT-CMAP) in 100% (57/57). ABP-CMAP was not recorded in patients in whom severe atrophy of the abductor pollicis brevis muscle was evident. As 2L-CMAP is maintained even in the most severe cases of CTS, the 2L-INT method is a valuable test for improving the accuracy of preoperative diagnosis in the electrophysiological diagnosis of CTS.

Morphological Changes in Anterior Horn Cells, Immunoreactivity to Neurotrophic Factors, and Neuronal Cell Death of Spinal Cord Lesions in the Spinal Hyperostotic Mouse (twy/twy) with Chronic Mechanical Cord Compression

We examined the morphology of spinal accessory motoneurons, immunoreactivity to brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-3, and reactive astrocytosis in 70 tiptoe-walking Yoshimura (twy/twy) mice that develop calcification at C1–C2 vertebral level compressing the spinal cord. At the level of compression, the area of neuronal soma, total length of dendrites, and numbers of wheat germ agglutinin-horseradish peroxidase (WGA-HRP)-labeled accessory motoneurons decreased significantly. Rostral to the compressive lesion, opposite findings were evidenced; enhanced BDNF and NT-3 immunoreactivities were evident in the anterior horn cells, increasing in response to a more severe degree of compression, with larger population of BDNF-positive astrocyte-like cells.

A large neurinoma originating from the anterior interosseous nerve.

We report an interesting case of a neurinoma originating from the anterior interosseous nerve. Magnetic resonance (MR) images showed an egg-shaped, well-circumscribed mass on the volar side of the forearm. On the enhanced three-dimensional computer tomography (3D-CT), it was clearly demonstrated that the tumour had arterial feeding from the anterior interosseous artery. The enhanced 3D-CT angiography was useful in the pre-operative diagnosis and surgical planning of peripheral neurinomas.

Spinal Cord Lesions in Spinal Hyperostotic Mouse (twy/twy) Simulating Ossification of the Posterior Longitudinal Ligament of the Cervical Spine

In the spinal hyperostotic mouse model (twy/twy), at the C1-C2 level developing calcification and ossification, the area of neuronal soma and the length of the neurites significantly decreased with a decrement in the motoneuron population. The compression significantly decreased the expression levels of BDNF and NT-3, trkB, and trkC compared with the levels in adjacent, less-compressed segments. On the other hand, at other spinal cord segments sustaining less compressive stress, enlargement of the neuronal soma and elongation of neurites were observed in association with increased expression of BDNF, NT-3, and the receptor proteins trkB and trkC. In 20-week-old twy mice, separation of the myelin sheath from the axon and axonal swelling with deformation were signifi cant in association of increased mmunoreactivity to neurofi lament protein and growth-associated protein 43. Targeted retrograde adenovirus-BDNF-gene in vivo delivery via the sternomastoid muscle prevented loss of anterior horn neurons at the site of spinal cord compression, enhanced the expression of BDNF, and increased the activities of choline acetyltransferase and acetylcholine esterase in motoneurons of the twy mouse spinal cord.