Viet Nguyen, MD

All Publications

• Incidence of Aicardi-Goutières syndrome and KCNT1-related epilepsy in Denmark. Molecular genetics and metabolism reports Møller, R. S., Zhao, L., Shoaff, J. R., Duno, M., Andersen, B. N., Nguyen, V., Fang, T. C., Kupelian, V., Thorén, R. 2022; 33: 100924

  Abstract

  To estimate the incidence of Aicardi-Goutières syndrome (AGS) and potassium sodium-activated channel subfamily T member 1 (KCNT1)-related epilepsy in Denmark and to characterize the patients diagnosed with AGS and KCNT1-related epilepsy.AGS and KCNT1-related epilepsy are 2 distinct rare genetic disorders. Due to the rarity of AGS and KCNT1-related epilepsy, the epidemiology remains unclear. The incidences for these diseases or the carriers with disease-related genetic variants remain unknown.This is a retrospective, non-interventional, population-based study using aggregate data from the Danish population register and hospital-based patient-level data in Denmark to identify persons with genetically confirmed AGS between January 2010 to December 2020 and KCNT1-related epilepsies between January 2012 to December 2020. Cases of these disorders were identified from in-hospital databases, and pathogenic variants were identified and confirmed by Sanger and/or whole exome (panel-based) sequencing. The incidence of AGS and KCNT1-related epilepsy were estimated in separate statistical analyses.A total of 7 AGS patients were identified. The mean age at AGS diagnosis was 19.4 months (median age 14 months). TREX1 (n < 5) and RNASEH2B (n ≥ 5) genes were reported with confirmed pathogenic variants. The birth incidence of AGS was <0.7600 per 100,000 live births. The average annual incidence rate was calculated as 0.0539 (95% CI: 0.0217-0.1111) per 100,000 persons per year in the total population < 18 years (n = 7); the average annual incidence rate was <0.7538 per 100,000 persons per year (n < 5) in the population < 12 months, and the average annual incidence rate in the population ≥ 12 months and < 18 years was <0.0406 per 100,000 persons per year (n < 5). A total of 14 KCNT1-related epilepsy cases were identified during the study period (n = 5 in 2016, remaining 9 cases in 2013 and 2015). The mean age at diagnosis was 20.6 years (median 19 years) for KCNT1 cases. A total of 8 cases (57.1%) were ≥ 18 years, and 6 (42.9%) were < 18 years at diagnosis. The phenotype autosomal dominant or sporadic sleep-related hypermotor epilepsy (ADSHE) (n = 10, 71.4%) was most reported; the remaining 4 cases had either epilepsy of infancy with migrating focal seizures (EIMFS) or an unclassifiable developmental and epileptic encephalopathy (DEE). The birth incidence of KCNT1-related epilepsy was ≤1.1205 per 100,000 live births. The average annual incidence rates per 100,000 persons per year during the study period were 0.0431 (95% confidence interval [CI]: 0.0236-0.0723; n = 14) in the overall population ≤ 50 years, 0.0568 (95% CI: 0.0209-0.1237; n = 6) in the population < 18 years, and 0.0365 (95% CI: 0.0157-0.0718; n = 8) in the population ≥ 18 and ≤ 50 years. There were 3 families with at least 2 cases diagnosed with KCNT1-related epilepsies (on average 3.3 cases per family), indicating 10 cases in total within the 3 families. All KCNT1 cases of ADSHE phenotype came from the 3 families. The higher incidence of older ages and ADSHE cases compared with previous KCNT1 studies is likely due to the capture of prevalent and familial previously undiagnosed cases. Excluding these family cases, the average annual incidence was 0.0123 (95% CI: 0.0034-0.0315, n = 4) per 100,000 persons per year in the population ≤ 50 years during 2012-2020.AGS and KCNT1-related epilepsy are particularly rare diseases. The annual average incidence rate of AGS was 0.0539 per 100,000 persons per year in the population < 18 years and birth incidence was <0.7600 per 100,000 live births during 2010-2020. The average annual incidence rate of KCNT1-related epilepsy was 0.0431 per 100,000 persons per year in the population ≤ 50 years and the birth incidence was ≤1.1205 per 100,000 live births during 2012-2020. Given similar healthcare systems and genetic pools, these findings may provide insight on the incidence of these rare diseases in the Nordics.

  View details for DOI 10.1016/j.ymgmr.2022.100924

  View details for PubMedID 36262748

  View details for PubMedCentralID PMC9574483

• Direct brainstem somatosensory evoked potentials for cavernous malformations. Journal of neurosurgery Le, S., Nguyen, V., Lee, L., Cho, S. C., Malvestio, C., Jones, E., Dodd, R., Steinberg, G., Lopez, J. 2021: 1-7

  Abstract

  OBJECTIVE: Brainstem cavernous malformations (CMs) often require resection due to their aggressive natural history causing hemorrhage and progressive neurological deficits. The authors report a novel intraoperative neuromonitoring technique of direct brainstem somatosensory evoked potentials (SSEPs) for functional mapping intended to help guide surgery and subsequently prevent and minimize postoperative sensory deficits.METHODS: Between 2013 and 2019 at the Stanford University Hospital, intraoperative direct brainstem stimulation of primary somatosensory pathways was attempted in 11 patients with CMs. Stimulation identified nucleus fasciculus, nucleus cuneatus, medial lemniscus, or safe corridors for incisions. SSEPs were recorded from standard scalp subdermal electrodes. Stimulation intensities required to evoke potentials ranged from 0.3 to 3.0 mA or V.RESULTS: There were a total of 1 midbrain, 6 pontine, and 4 medullary CMs-all with surrounding hemorrhage. In 7/11 cases, brainstem SSEPs were recorded and reproducible. In cases 1 and 11, peripheral median nerve and posterior tibial nerve stimulations did not produce reliable SSEPs but direct brainstem stimulation did. In 4/11 cases, stimulation around the areas of hemosiderin did not evoke reliable SSEPs. The direct brainstem SSEP technique allowed the surgeon to find safe corridors to incise the brainstem and resect the lesions.CONCLUSIONS: Direct stimulation of brainstem sensory structures with successful recording of scalp SSEPs is feasible at low stimulation intensities. This innovative technique can help the neurosurgeon clarify distorted anatomy, identify safer incision sites from which to evacuate clots and CMs, and may help reduce postoperative neurological deficits. The technique needs further refinement, but could potentially be useful to map other brainstem lesions.

  View details for DOI 10.3171/2021.7.JNS21317

  View details for PubMedID 34740189

• Electromyographic Analysis of Grip ORTHOPEDICS Fox, P. M., Oliver, J. D., Viet Nguyen, Hentz, V. R., Curtin, C. M. 2019; 42 (6): E555–E558

  Abstract

  This prospective cohort study used video electromyography synchronized analysis to determine the dynamic use of extrinsic and intrinsic finger flexion during grasp. Light fist formation primarily involved the flexor digitorum profundus with either the flexor digitorum superficialis or intrinsics. In contrast, both the flexor digitorum superficialis and intrinsics were recruited in all tight fist video electromyography. However, the sequence of recruitment differed between patients in tight fist formation. Injured patients demonstrated a unique pattern of recruitment based on injury. The authors conclude that the flexor digitorum profundus is the workhorse in composite fist formation but the roles of the flexor digitorum superficialis and the intrinsic muscles are less consistent across patients. [Orthopedics. 2019; 42(6):e555-e558.].

  View details for DOI 10.3928/01477447-20190812-06

  View details for Web of Science ID 000498511000012

  View details for PubMedID 31408520

• Superselective methohexital challenge prior to intracranial endovascular embolization JOURNAL OF CLINICAL NEUROSCIENCE Bican, O., Cho, C., Suarez-Roman, A., Viet Nguyen, Lee, L., Le, S., Heit, J., Dodd, R., Lopez, J. 2019; 63: 68–71

  View details for DOI 10.1016/j.jocn.2019.01.051

  View details for Web of Science ID 000466249000013

• Driving Ability Correlated with Severity of Polyneuropathy Lopez, J., Cho, A., Nguyen, V., Lee, L., Le, S., Cho, S. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000475965903017

• Superselective methohexital challenge prior to intracranial endovascular embolization. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Bican, O., Cho, C., Suarez-Roman, A., Nguyen, V., Lee, L., Le, S., Heit, J., Dodd, R., Lopez, J. 2019

  Abstract

  Pharmacologic provocative testing (PT) and intraoperative neurophysiologic monitoring (IONM) both mitigate and predict risks associated with endovascular embolization procedures. We present a series of patients undergoing endovascular intracranial embolization predominantly for AVMs both under general anesthesia and awake with the use of IONM. We reviewed our database to identify all patients undergoing endovascular procedures between January 1, 2014 and January 1, 2016. Awake patients were tested with SSEP, EEG and real time neurologic examination while TcMEPs were performed in all anesthetized patients. BAEPs were performed in anesthetized patients if indicated. Methohexital was administered as an injection at a dose of 5 mg or 10 mg and repeat testing was performed if needed.Sixty-three endovascular procedures that met criteria were performed in 32 patients. 54 procedures in 28 patients were performed under general anesthesia, 9 procedures in 4 patients were performed in wakefulness. PT was negative in 61 procedures and subsequently completed embolizations without neurological sequelae. In two cases, the testing was positive and the procedure was terminated without embolization in one patient. The other patient underwent embolization at an alternative site without repeat PT. There were no new postoperative neurologic deficits after any of these procedures. Specificity of PT was 100% as none of the patients with a negative provocative test developed a new postoperative neurologic deficit after embolization. To our knowledge, this is the first review of PT with the use of neurophysiologic IONM techniques under general anesthesia. These data suggest a high specificity comparable to awake testing.

  View details for PubMedID 30772199

• Intraoperative Transcranial Motor-evoked Potential Stimulation Does Not Seem to Cause Seizures. Journal of neurosurgical anesthesiology Burbridge, M. A., Nguyen, V. n., Min, J. G., Jaffe, R. A., Ahuja, B. n., Shah, A. D., Lee, L. H., Cho, C. n., Sandoval, B. n., López, J. R. 2019

  Abstract

  Intraoperative neurophysiological monitoring is of critical importance in evaluating the functional integrity of the central nervous system during surgery of the central or peripheral nervous system. In a large recent study, transcranial motor-evoked potentials (TcMEPs) were found to be associated with a 0.7% risk of inducing a seizure as diagnosed by clinical observation and electromyography in patients having general anesthesia with intravenous anesthetics. The gold standard for seizure diagnosis, however, is electroencephalography (EEG). The aim of this single-institution retrospective study is to ascertain the risk of intraoperative seizures detected using EEG during surgeries in adult patients undergoing intraoperative monitoring with TcMEPs.The authors retrospectively reviewed the intraoperative EEG records of 1175 patients anesthetized with a variety of anesthetic agents, including volatile and intravenous anesthetics, to ascertain the rate of EEG-diagnosed seizures attributable to TcMEPs.Our analysis did not reveal a single seizure event attributable to TcMEPs in 1175 patients.The intraoperative use of TcMEPs does not seem to cause seizures.

  View details for DOI 10.1097/ANA.0000000000000671

  View details for PubMedID 31876633

• Positive pharmacologic provocative testing with methohexital during cerebral arteriovenous malformation embolization. Clinical imaging Bican, O., Cho, C., Lee, L., Nguyen, V., Le, S., Heit, J., Lopez, J. 2018; 51: 155–59

  Abstract

  A middle-aged patient underwent staged endovascular embolization of a Spetzler-Martin grade V right parietal arteriovenous malformation(AVM).In the fifth endovascular embolization, after methohexital 10 mg injection into a right posterior choroidal artery feeding the AVM nidus, there was an immediate change in the electroencephalogram (EEG) with simultaneous loss of motor evoked potentials (MEPs) in the bilateral upper and lower extremities and a delayed change in somatosensory evoked potential responses (SSEPs). No embolization was made and procedure was terminated. This case demonstrates the utility of intraoperative neurophysiologic monitoring (IONM) with pharmacologic provocative testing in predicting and mitigating the risks prior to the proposed embolization.

  View details for PubMedID 29501883

• Retrospective Waveform Analysis of Transcranial Motor Evoked Potentials (MEP) to Identify Early Predictors of Impending Motor Deficits in Spinal Surgeries. The Neurodiagnostic journal Le, S., Nguyen, V., Ekwueme, A. C., Cho, S. C., Lee, L., López, J. 2017; 57 (1): 53-68

  Abstract

  Although there are guidelines analyzing transcranial motor evoked potentials (MEP) waveform criteria, they vary widely and are not applied universally during intraoperative neurophysiologic monitoring (IONM). The objective is to generate hypotheses to identify early and reliable MEP waveform characteristics prior to complete loss of MEP to predict impending motor spinal cord injuries during spinal surgeries. The ultimate goal is to enhance real-time feedback to prevent injury or detect reversible spinal cord damage.Fifteen true positive cases of persistent intraoperative MEP loss and new postoperative motor deficits were retrospectively identified from 2011 to 2013. Waveform characteristics of latency, amplitude, duration, phases, and area-under-the-curve (AUC) were measured, and an intraoperative spinal cord index (ISCI) was calculated for 5 traces prior to complete MEP loss. ISCI = [amplitude x duration x (phases+1) x AUC]/latency.Out of 22 muscles in 15 cases, latency increased in 2, duration decreased in 12, amplitude decreased in 13, AUC decreased in 13, and ISCI decreased in 14. In 11 out of 15 cases (73%), ISCI dropped > 40% in at least one muscle before MEP were completely lost. Thirteen cases had concurrent somatosensory evoked potentials (SSEP) changes, 9 out of 13 had > 50% decrease in SSEP: 2 out of 9 changed before MEP, 5 out of 9 simultaneously, and 2 out of 9 after.In these cases of motor injury, smaller and simpler MEP waveforms preceded complete loss of signal. An ISCI 40% drop could be tested as a warning threshold for impending motor compromise in future prospective studies and lead to eventual standardization to predict irreversible postoperative deficits.

  View details for DOI 10.1080/21646821.2017.1257330

  View details for PubMedID 28436812

• Diagnostic Utility of Intraoperative Neurophysiological Monitoring for Intramedullary Spinal Cord Tumors: Systematic Review and Meta-Analysis. Clinical spine surgery Azad, T. D., Pendharkar, A. V., Nguyen, V. n., Pan, J. n., Connolly, I. D., Veeravagu, A. n., Popat, R. n., Ratliff, J. K., Grant, G. A. 2017

  Abstract

  Systematic review and meta-analysis.The aim of this study was to systematically evaluate the diagnostic utility of intraoperative neurophysiological monitoring (IONM) for detecting postoperative injury in resection of intramedullary spinal cord tumors (IMSCT).Surgical management of IMSCT can involve key neurological and vascular structures. IONM aims to assess the functional integrity of susceptible elements in real time. The diagnostic value of IONM for ISMCT has not been systematically evaluated.We performed a systematic review of the PubMed and MEDLINE databases for studies investigating the use of IONM for IMSCT and conducted a meta-analysis of diagnostic capability.Our search produced 257 citations. After application of exclusion criteria, 21 studies remained, 10 American Academy of Neurology grade III and 11 American Academy of Neurology grade IV. We found that a strong pooled mean sensitivity of 90% [95% confidence interval (CI), 84-94] and a weaker pooled mean specificity of 82% (95% CI, 70-90) for motor-evoked potential (MEP) recording changes. Somatosensory-evoked potential (SSEP) recording changes yielded pooled sensitivity of 85% (95% CI, 75-91) and pooled specificity of 72% (95% CI, 57-83). The pooled diagnostic odds ratio for MEP was 55.7 (95% CI, 26.3-119.1) and 14.3 (95% CI, 5.47-37.3) for SSEP. Bivariate analysis yielded summary receiver operative characteristic curves with area under the curve of 91.8% for MEPs and 86.3% for SSEPs.MEPs and SSEPs appear to be more sensitive than specific for detection of postoperative injury. Patients with perioperative neurological deficits are 56 times more likely to have had changes in MEPs during the procedure. We observed considerable variability in alarm criteria and interventions in response to IONM changes, indicating the need for prospective studies capable of defining standardized alarm criteria and responses.

  View details for PubMedID 28650882

• Fentanyl-induced suppression of transcranial Motor Evoked Potentials (tcMEPs) Anaesthesia Cases Bican, O., López, J., Cho, S. C., Nguyen, V., Le, S., Lee, L. 2016; 0241
• In Vivo Imaging of Human Sarcomere Twitch Dynamics in Individual Motor Units. Neuron Sanchez, G. N., Sinha, S., Liske, H., Chen, X., Nguyen, V., Delp, S. L., Schnitzer, M. J. 2015; 88 (6): 1109-20

  Abstract

  Motor units comprise a pre-synaptic motor neuron and multiple post-synaptic muscle fibers. Many movement disorders disrupt motor unit contractile dynamics and the structure of sarcomeres, skeletal muscle's contractile units. Despite the motor unit's centrality to neuromuscular physiology, no extant technology can image sarcomere twitch dynamics in live humans. We created a wearable microscope equipped with a microendoscope for minimally invasive observation of sarcomere lengths and contractile dynamics in any major skeletal muscle. By electrically stimulating twitches via the microendoscope and visualizing the sarcomere displacements, we monitored single motor unit contractions in soleus and vastus lateralis muscles of healthy individuals. Control experiments verified that these evoked twitches involved neuromuscular transmission and faithfully reported muscle force generation. In post-stroke patients with spasticity of the biceps brachii, we found involuntary microscopic contractions and sarcomere length abnormalities. The wearable microscope facilitates exploration of many basic and disease-related neuromuscular phenomena never visualized before in live humans. VIDEO ABSTRACT.

  View details for DOI 10.1016/j.neuron.2015.11.022

  View details for PubMedID 26687220

• In Vivo Imaging of Human Sarcomere Twitch Dynamics in Individual Motor Units NEURON Sanchez, G. N., Sinha, S., Liske, H., Chen, X., Viet Nguyen, V., Delp, S. L., Schnitzer, M. J. 2015; 88 (6): 1109-1120

  Abstract

  Motor units comprise a pre-synaptic motor neuron and multiple post-synaptic muscle fibers. Many movement disorders disrupt motor unit contractile dynamics and the structure of sarcomeres, skeletal muscle's contractile units. Despite the motor unit's centrality to neuromuscular physiology, no extant technology can image sarcomere twitch dynamics in live humans. We created a wearable microscope equipped with a microendoscope for minimally invasive observation of sarcomere lengths and contractile dynamics in any major skeletal muscle. By electrically stimulating twitches via the microendoscope and visualizing the sarcomere displacements, we monitored single motor unit contractions in soleus and vastus lateralis muscles of healthy individuals. Control experiments verified that these evoked twitches involved neuromuscular transmission and faithfully reported muscle force generation. In post-stroke patients with spasticity of the biceps brachii, we found involuntary microscopic contractions and sarcomere length abnormalities. The wearable microscope facilitates exploration of many basic and disease-related neuromuscular phenomena never visualized before in live humans. VIDEO ABSTRACT.

  View details for DOI 10.1016/j.neuron.2015.11.022

  View details for Web of Science ID 000368443900008

• Neuromonitoring: EMG, SSEP and MEP Neurosurgery Tricks of the Trade: Spine and Peripheral Nerves Nguyen, V., Lopez, J. R. edited by Nader, R., Berta, S. Thieme. 2014; 1st edition: Chapter 88
• Peripheral Nerve Surgery A Practical Approach to Neurophysiologic Intraoperative Monitoring Nguyen, V., Jones, E. edited by Husain, A. M. Demos Medical Publishing. 2014; 2nd edition: 163–179
• Detection of inferolateral trunk syndrome by neuromonitoring during catheter angiography with provocative testing. Journal of neurointerventional surgery Le, S., Dodd, R., López, J., Nguyen, V., Cho, S. C., Lee, L. 2013; 5 (2)

  Abstract

  It is not uncommon that endovascular balloon test occlusion (BTO) is performed to assess collateral blood flow and risk of injury of permanent occlusion of the internal carotid artery (ICA). This case is the first reported of detection and reversal of the inferolateral trunk (ILT) syndrome in an awake patient during provocative BTO; prompt recognition of the syndrome effectively prevented permanent neurologic deficits.The case of a 42-year-old woman is reported who had a left sphenoid wing meningioma with extension into the cavernous sinus and who underwent awake catheter angiography with provocative BTO of the ICA. Serial examinations by intraoperative monitoring neurologists and neurointerventionalists detected acute progressive left retro-orbital pressure followed by sudden inability to adduct the left eye, or a left medial rectus palsy, indicative of the ILT syndrome which led to immediate balloon deflation and resolution of the deficits. The hypothesis was that hypoperfusion of the ILT, an arterial branch of the ICA which provides blood supply to several cranial nerves (CN) III, CN V1 and CN V2, caused her acute symptoms.Although cerebral ischemia is a well known complication of endovascular procedures, CN ischemia is a rare potential risk. Knowledge of cerebrovascular anatomy and serial examinations prevented neurologic deficits; this case underscores the added utility of examinations by intraoperative monitoring neurologists and interdisciplinary collaboration.

  View details for DOI 10.1136/neurintsurg-2011-010236

  View details for PubMedID 22345146