Identification of a Biallelic Missense Variant in Gasdermin D (c.823G > C, p.Asp275His) in a Patient of Atypical Gorham-Stout Disease in a Consanguineous Family.

Gorham-Stout disease (GSD), also called vanishing bone disease, is a rare osteolytic disease, frequently associated with lymphangiomatous tissue proliferation. The causative genetic background has not been noted except for a case with a somatic mutation in KRAS. However, in the present study, we encountered a case of GSD from a consanguineous family member. Whole-exome sequencing (WES) analysis focusing on rare recessive variants with zero homozygotes in population databases identified a homozygous missense variant (c.823G > C, p.Asp275His) in gasdermin D (GSDMD) in the patient and heterozygous in his unaffected brother. Because this variant affects the Asp275 residue that is involved in proteolytic cleavage by caspase-11 (as well as -4 and -5) to generate an activating p30 fragment required for pyroptotic cell death and proinflammation, we confirmed the absence of this cleavage product in peripheral monocytic fractions from the patient. A recent study indicated that a shorter p20 fragment, generated by further cleavage at Asp88, has a cell-autonomous function to suppress the maturation of osteoclasts to resorb bone matrix. Thus, the present study suggests for the first time the existence of hereditary GSD cases or novel GSD-like diseases caused by GSDMD deficiency. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Locking of the Distal Radioulnar Joint Caused by Dorsal Tear of the Triangular Fibrocartilage Complex: A Case Report.

CASE: We encountered a case of locking of the distal radioulnar joint after a traumatic injury that restricted the supination and pronation of the wrist. The locking was released surgically with a good 2-year outcome. We found a tear between the dorsal aspect of the joint capsule and the triangular fibrocartilage complex (TFCC). The tear allowed the TFCC to displace volarly and become entrapped against the volar aspect of the ulnar head. CONCLUSION: The open approach facilitated visualization and understanding of this unusual injury pattern and allowed direct repair. Joint incongruity may not occur despite a locked joint.

Evaluation of neural activity by magnetospinography with 3D sensors.

OBJECTIVE: Magnetospinography (MSG) has been developed for clinical application and is expected to be a novel neurophysiological examination. Here, we used an MSG system with sensors positioned in three orthogonal directions to record lumbar canal evoked magnetic fields (LCEFs) in response to peripheral nerve stimulation and to evaluate methods for localizing spinal cord lesions. METHODS: LCEFs from the lumbar area of seven rabbits were recorded by the MSG system in response to electrical stimulation of a sciatic nerve. LCEFs and lumbar canal evoked potentials (LCEPs) were measured before and after spinal cord compression induced by a balloon catheter. The lesion positions were estimated using LCEPs and computationally reconstructed currents corresponding to the depolarization site. RESULTS: LCEFs were recorded in all rabbits and neural activity in the lumbar spinal cord could be visualized in the form of a magnetic contour map and reconstructed current map. The position of the spinal cord lesion could be estimated by the LCEPs and reconstructed currents at the depolarization site. CONCLUSIONS: MSG can visualize neural activity in the spinal cord and localize the lesion site. SIGNIFICANCE: MSG enables noninvasive assessment of neural activity in the spinal canal using currents at depolarization sites reconstructed from LCEFs.

Ulnar neuropathy at the elbow in 413 Japanese patients: An assessment of pathological elbow lesions and neurological severity.

BACKGROUND: Various pathological elbow lesions are often complicated with ulnar neuropathy at the elbow (UNE), although the precise pathology, incidence, and clinical and neurological features of these lesions have not been identified. We therefore investigated elbow pathology and neurological severity in Japanese patients with UNE. METHODS: The medical records of 457 Japanese UNE patients who were surgically treated among 6 hospitals were retrospectively examined. Eligible patients had UNE diagnosed by physical findings and nerve conduction studies according to the criteria of the American Association of Electrodiagnostic Medicine. The elbows were analyzed with regard to age, gender, occupation, pathology at the elbow, and severity of nerve palsy. RESULTS: A total of 398 patients with 413 UNE elbows of a mean age of 63 years (range: 15-87) met the inclusion criteria. UNE elbows were predominantly in male patients (69.0%). Overall, 310 elbows (75.1%) had 1 or more elbow lesions: 238 elbows (76.8%) had a single lesion and 72 elbows (23.3%) had 2 or more lesions. The most common lesion was primary elbow osteoarthritis (EOA) occurring in 54.5% of elbows, followed next by medial elbow ganglion in 8.5% and cubitus valgus in 6.5%. Most elbows with medial elbow ganglion or cubitus valgus were associated with EOA. Entrapment sites were at the cubital tunnel in 84.5%-91.3% of UNE elbows, regardless of an association with elbow lesion. The incidence of McGowan grade III lesion was 50.8% in elbows with primary EOA, which was higher than the 35.0% in elbows with no lesion. CONCLUSIONS: This study revealed that UNE had various isolated or combined elbow lesions. In Japanese UNE, primary or secondary EOA was found in 62.2% of cases and severe motor weakness was noted in 47.2%. The incidences of EOA and severe ulnar nerve palsy in the Japanese UNE are higher than those in Caucasians. LEVEL OF EVIDENCE: Level IV; Prognostic-Investigating the effect of a patient characteristic on the outcome of a disease; Case series.

Magnetospinography visualizes electrophysiological activity in the cervical spinal cord.

Diagnosis of nervous system disease is greatly aided by functional assessments and imaging techniques that localize neural activity abnormalities. Electrophysiological methods are helpful but often insufficient to locate neural lesions precisely. One proposed noninvasive alternative is magnetoneurography (MNG); we have developed MNG of the spinal cord (magnetospinography, MSG). Using a 120-channel superconducting quantum interference device biomagnetometer system in a magnetically shielded room, cervical spinal cord evoked magnetic fields (SCEFs) were recorded after stimulation of the lower thoracic cord in healthy subjects and a patient with cervical spondylotic myelopathy and after median nerve stimulation in healthy subjects. Electrophysiological activities in the spinal cord were reconstructed from SCEFs and visualized by a spatial filter, a recursive null-steering beamformer. Here, we show for the first time that MSG with high spatial and temporal resolution can be used to map electrophysiological activities in the cervical spinal cord and spinal nerve.

Efficacy of biphasic transcranial electric stimulation in intraoperative motor evoked potential monitoring for cervical compression myelopathy.

STUDY DESIGN: Retrospective analysis of prospectively collected data from consecutive patients undergoing 2 methods of transcranial electrical motor evoked potential (TCE-MEP) monitoring during cervical spine surgery. OBJECTIVE: To investigate the efficacy of biphasic transcranial electric stimulation, the deviation rate, amplitude of TCE-MEPs, complications, and sensitivity and specificity of TCE-MEP monitoring were compared between the biphasic and conventional monophasic stimulation methods. SUMMARY OF BACKGROUND DATA: With biphasic stimulation, unlike monophasic stimulation, measurement time can be reduced considerably because a single stimulation elicits bilateral responses almost simultaneously. However, no study has yet reported a detailed comparison of the 2 methods. METHODS: Examination 1: Amplitude and derivation rate of TCE-MEPs was compared for monophasic and biphasic stimulation in the same 31 patients with cervical compression myelopathy. Examination 2: Sensitivity, specificity, and complications of TCE-MEP monitoring were compared in 200 patients with cervical compression myelopathy who received monophasic or biphasic stimulation (100 patients each) during intraoperative monitoring. RESULTS: Examination 1: Derivation rates of biphasic stimulation in the deltoid, biceps brachii, abductor digiti minimi, and flexor hallucis brevis muscles were the same or higher than for monophasic stimulation. TCE-MEP amplitudes elicited by biphasic stimulation compared with monophasic stimulation were significantly larger in the biceps (paired t, P < 0.0001), but similar in the other 3 muscles. Examination 2: In the biphasic and monophasic stimulation groups, warnings were issued to surgeons in 10 and 11 cases, for a sensitivity of 100% for both groups and specificity of 97.8% and 96.7%, respectively. No complications related to stimulation were observed in any of the 200 patients. CONCLUSION: Biphasic stimulation had similar or higher derivation rates and equivalent sensitivity and specificity than monophasic stimulation. No complications were observed for either stimulation method. Biphasic stimulation is an effective TCE-MEP monitoring method for cervical spine surgery that may also reduce measurement time. LEVEL OF EVIDENCE: 4.

Warning thresholds on the basis of origin of amplitude changes in transcranial electrical motor-evoked potential monitoring for cervical compression myelopathy.

STUDY DESIGN: A retrospective analysis of prospectively collected data from consecutive patients undergoing transcranial electrical motor-evoked potential (TCE-MEP: compound muscle action potentials) monitoring during cervical spine surgery. OBJECTIVE.: To divide the warning threshold of TCE-MEP amplitude changes on the basis of origin into the spinal tract and spinal segments and decide warning thresholds for each. SUMMARY OF BACKGROUND DATA: The parameter commonly used for the warning threshold in TCE-MEP monitoring is wave amplitude, but amplitude changes have not been examined by anatomical origin. METHODS: Intraoperative TCE-MEP amplitude changes were reviewed for 357 patients with cervical myelopathy. Most of the patients were monitored by transcranial electrical stimulated spinal-evoked potential combined with TCE-MEP. The warning threshold of TCE-MEP was taken as waveform disappearance. For each patient, amplitude changes were separated, according to origin, into the spinal tract and spinal segments and compared with clinical outcome. RESULTS: Assessable TCE-MEP waves were obtained in 350 cases. Disappearance of TCE-MEP waves, which were innervated by the spinal levels exposed to the surgical invasion, was seen in 11 cases. Disappearance of TCE-MEPs, which were innervated by the spinal levels inferior to them, was seen in 43 cases. There was no postoperative motor deficit in those cases. However, such deficits caused by spinal segment injury were seen in 2 cases, which showed that intraoperative amplitude decreased to 4.5% and 27%. CONCLUSION: If we had established the warning threshold as 30% of the control amplitude, we would likely have prevented both cases of postoperative motor deficits, but 106 (30.3%) cases would have become positive cases. If we had established the warning threshold separately as wave disappearance for the spinal tract and 30% of the control amplitude for the spinal segments, sensitivity and specificity would have been 100% and 83.7%, respectively. Dividing the warning threshold on the basis of origin of amplitude changes could reduce false-positive cases and prevent intraoperative injuries.

Conductive neuromagnetic fields in the lumbar spinal canal.

OBJECTIVE: To measure neuromagnetic evoked fields in the lumbar spinal canal. METHODS: Using a newly developed superconducting quantum interference device (SQUID) fluxmeter, neuromagnetic fields of 5 healthy male volunteers were measured at the surface of the lower back after stimulation of the tibial nerves at the ankles. For validation, we inserted a catheter-type electrode percutaneously in the lumbar epidural space in 2 of the subjects and measured cauda equina action potentials after tibial nerve stimulation. RESULTS: Neuromagnetic fields propagating from the intervertebral foramina into the spinal canal were measured, and the latencies of the magnetic fields corresponded largely with those of the cauda equina action potentials. CONCLUSIONS: We successfully measured ascending neuromagnetic fields originating at the nerve root and the cauda equina with high spatial resolution. Future studies will determine whether neuromagnetic field measurement of the lumbar spine can be a useful diagnostic method for the identification of the disordered site in spinal nerves. SIGNIFICANCE: We successfully measured neuromagnetic fields in the lumbar spinal canal, which have previously been difficult to verify. Future studies will determine whether neuromagnetic field measurement of the lumbar spine can be a useful diagnostic method for identifying disorders of spinal nerves.

Diagnosis of incomplete conduction block of spinal cord from skin surface using spinal cord evoked magnetic fields.

BACKGROUND: We previously reported the usefulness of neuromagnetic recordings for the diagnosis of disorders in peripheral nerves or the spinal cord. However, there have been no reports on incomplete conduction block of the spinal cord, which is clinically common in conditions such as cervical myelopathy. Here, we estimated the usefulness of measuring spinal cord evoked magnetic fields for evaluating incomplete conduction block. METHODS: Incomplete conduction block models of the spinal cord of the rabbit were established using a Fogarty balloon catheter that was inserted into the epidural space of the cervical spine. Electrical stimuli were applied to the lower thoracic spinal cord with an epidural catheter electrode. Spinal cord evoked potentials were recorded using epidural electrodes. Spinal cord evoked magnetic fields were recorded over the skin surface of the neck using a biomagnetometer. RESULTS: The decrease in the conduction velocity and amplitude at the compression site could be detected by spinal cord evoked potentials from the epidural space, confirming the spinal cord lesion. The waveforms of the magnetic fields showed a biphasic configuration. The distribution of magnetic fields showed a characteristic quadrupolar pattern propagating from caudal to cranial. After compression, the amplitude and the conduction velocity of the magnetic fields decreased, and the distribution of magnetic fields were attenuated and decelerated near the compression site especially in the trailing magnetic fields. Diagnosis of the incomplete conduction block was thus possible. CONCLUSIONS: We report the first measurement of the spinal cord evoked magnetic field in the intact spinal cord from the skin surface and that it can be applied to incomplete conduction block of the injured spinal cord. The use of a biomagnetometer is promising as a less-invasive method for clinically evaluating spinal cord function.

Functional imaging of spinal cord electrical activity from its evoked magnetic field.

This paper investigates dynamic source imaging of the spinal cord electrophysiological activity from its evoked magnetic field by applying the spatial filter version of standardized low-resolution brain electromagnetic tomography (sLORETA). Our computer simulation shows that the sLORETA-based spatial filter can reconstruct the four current sources typically associated with the elicitation of the spinal cord evoked magnetic field (SCEF). The results from animal experiments show that significant changes in the latency and intensity of the reconstructed volume current arise near the location of the artificial incomplete conduction block. The results from the human SCEF show that the SCEF source imaging can visualize the dynamics of the volume currents and other nerve electrical activity propagating along the human spinal cord. These experimental results demonstrate the potential of SCEF source imaging as a future clinical tool for diagnosing cervical spinal cord disorders.