Relationships between the global symptom score and electrophysiological findings after surgical release for carpal tunnel syndrome: Indications and outcomes.

PURPOSE: Regarding surgical indications for carpal tunnel syndrome (CTS), the hypothesis that the recovery processes of subjective symptoms differ among pain, sensory, and motor symptoms and correlate with recovery in objective nerve conduction studies was examined in the present study. METHODS: The global symptom score (GSS) is a method used to assess clinical outcomes and covers subjective symptoms, including pain (pain and nocturnal awakening), sensory (numbness and paresthesia), and motor (weakness/clumsiness) symptoms. The relationships between long-term changes in GSS and recovery in nerve conduction studies were investigated. RESULTS: Forty patients (40 hands) were included (mean age 65 years; 80% female; 68% with moderate CTS: sensory nerve conduction velocity < 45 m/s and motor nerve distal latency > 4.5 ms). Pain and nocturnal awakening rapidly subsided within 1 month after surgery and did not recur in the long term (median 5.6 years). Paresthesia significantly decreased 3 months after surgery and in the long term thereafter. Weakness/clumsiness significantly decreased at 1 year. Sensory nerve distal latency, conduction velocity, and amplitude significantly improved 3 months and 1 year after surgery, and correlated with nocturnal awakening in the short term (3 months) in moderate CTS cases. The patient satisfaction rate was 91%. CONCLUSION: Rapid recovery was observed in pain and nocturnal awakening, of which nocturnal awakening correlated with the recovery of sensory nerve conduction velocity. Patients with pain symptoms due to moderate CTS may benefit from surgical release.

Other median neuropathies.

Median mononeuropathy is common, with carpal tunnel syndrome the most frequently encountered acquired mononeuropathy in clinical practice. However, other disorders of the median nerve and many known anatomical variants can lead to misdiagnosis and unexpected surgical complications if their presence is not correctly identified. A number of inherited and acquired disorders can affect the median nerve proximal to the wrist, alone or accompanied by other affected peripheral nerves. Recognizing other disorders that can masquerade as median mononeuropathies can avoid misdiagnosis and misguided management. This chapter explores median nerve anatomical variants, disorders, and lesions, emphasizing the need for careful examination and electrodiagnostic study in the localization of median neuropathy.

Delays in latencies of median-nerve evoked magnetic fields in patients with succinic semialdehyde dehydrogenase deficiency.

OBJECTIVE: Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a genetic disorder resulting in abnormal regulation of γ-aminobutyric acid, lipid metabolism, and myelin biogenesis, leading to ataxia, seizures, and cognitive impairment. Since the myelin sheath is thinner in a murine model of SSADHD compared to a wild type, we hypothesized that this also holds for human brain. We tested whether the conduction velocity in the somatosensory pathway is accordingly delayed. METHODS: Somatosensory evoked magnetic fields (SEF) produced by transcutaneous electrical stimulation of the median nerve were measured in 13 SSADHD patients, 11 healthy and 14 disease controls with focal epilepsy. The peak latencies of the initial four components (M1, M2, M3 and M4) were measured. RESULTS: The SEF waveforms and scalp topographies were comparable across the groups. The latencies were statistically significantly longer in the SSADHD group compared to the two controls. We found these latencies for the SSADHD, healthy and disease controls respectively to be: M1: (21.9 ± 0.8 ms [mean ± standard error of the mean], 20.4 ± 0.6 ms, and 21.0 ± 0.4 ms) (p < 0.05); M2: (36.1 ± 1.0 ms, 33.1 ± 0.6 ms, and 32.1 ± 1.1 ms) (p < 0.005); M3: (62.5 ± 2.4 ms, 54.7 ± 2.0 ms, and 49.9 ± 1.8 ms) (p < 0.005); M4: (86.2 ± 2.3 ms, 78.8 ± 2.8 ms, and 73.5 ± 2.9 ms) (p < 0.005). CONCLUSIONS: The SEF latencies are delayed in patients with SSADHD compared with healthy controls and disease controls. SIGNIFICANCE: This is the first study that compares conduction velocities in the somatosensory pathway in SSADHD, an inherited disorder of GABA metabolism. The longer peak latency implying slower conduction velocity supports the hypothesis that myelin sheath thickness is decreased in SSADHD.

Utility of shear wave elastography and high-definition color for diagnosing carpal tunnel syndrome.

OBJECTIVE: The diagnostic values of measuring median nerve (MN) stiffness and vascularity with shear wave elastography (SWE) and high-definition (HD) color were investigated in carpal tunnel syndrome (CTS). METHODS: Seventy patients (123 wrists) with CTS and thirty-five healthy volunteers (70 wrists) were enrolled. Based on nerve conduction studies (NCS), the patients were subdivided into NCS-negative, mild-to-moderate, and severe CTS groups. MN and abductor pollicis brevis (APB) SWE and MN HD color were performed on a longitudinal plane. RESULTS: The mild-to-moderate and severe CTS groups showed increased MN stiffness at the wrist and MN stiffness ratio (wrist-to forearm) compared with the control (p < 0.001). The NCS-negative CTS group showed increased MN stiffness at the wrist (p = 0.022) and MN stiffness ratio (p = 0.032) compared with the control. The severe CTS group showed increased MN stiffness at the wrist compared with the mild-to-moderate CTS group (p = 0.034). The cutoff-values in diagnosing NCS-confirmed CTS were 50.12 kPa for MN stiffness at the wrist, 1.91 for MN stiffness ratio, and grade 1 for HD color. CONCLUSIONS: SWE and HD color are good supportive tools in diagnosing and assessing severity in CTS. SIGNIFICANCE: SWE and HD color demonstrated that MN in CTS was associated with increased stiffness and hypervascularity.

Application of digital infrared thermography for carpal tunnel syndrome evaluation.

We investigated the thermographic findings of carpal tunnel syndrome (CTS). We enrolled 304 hands with electrodiagnostically identified CTS and 88 control hands. CTS hands were assigned to duration groups (D1, < 3 months; D2, 3‒6 months; D3, 6‒12 months; D4, ≥ 12 months) and severity groups (S1, very mild; S2, mild; S3, moderate; S4, severe). The temperature difference between the median and ulnar nerve territories (ΔM-U territories) decreased as CTS duration and severity increased. Significant differences in ΔM-U territories between the D1 and D3, D1 and D4, D2 and D4, and S1 and S4 groups (P = 0.003, 0.001, 0.001, and < 0.001, respectively) were observed. Thermal anisometry increased as CTS duration and severity increased. Significant differences in thermal anisometry between the D1 and D4 as well as the D2 and D4 groups (P = 0.005 and 0.04, respectively) were noted. Thermal anisometry was higher in the S4 group than in the S1, S2, and S3 groups (P = 0.009, < 0.001, and 0.003, respectively). As CTS progresses, skin temperature tends to decrease and thermal variation tends to increase in the median nerve-innervated area. Thermographic findings reflect the physiological changes of the entrapped median nerve.

Acute carpal tunnel syndrome: Clinical, electromyographic, and ultrasound features in 25 patients.

BACKGROUND: The acute presentation of carpal tunnel syndrome (CTS) is rare. When symptoms start acutely with no obvious causes, ultrasound (US) imaging may provide clues to the etiology. OBJECTIVE: This study describes the clinical, electromyographic, and US findings in 25 patients presenting with acute CTS (ACTS). METHODS: In this analysis, of the patients referred for electrodiagnostic confirmation of CTS over the past decade, 25 had an acute onset of symptoms. All patients underwent EMG/NCV and US of the median nerve at the carpal tunnel and forearm. RESULTS: Of the 25 cases with ACTS, 5 (20%) had bilateral involvement leading to the total hands studied to 30. In 14 (56%) patients, an inciting event was identified as a possible cause of ACTS. In 11 (44%) patients without an antecedent event, 7 (64%) had a persistent median artery (PMA) detected by US. Electrodiagnostic studies showed prolonged distal motor latency with normal motor conduction velocity proximal to the carpal tunnel in 24 (80%) of 30 hands, 6 (20%) hands showed absent compound muscle action potentials over the abductor pollicis brevis (APB), and 22 (73%) hands had absent sensory potentials. Denervation changes were seen in the APB in 13 (43%) hands, and motor unit potentials were absent in 6 (20%) hands. Sixteen (64%) patients underwent a carpal tunnel release for severe symptoms. CONCLUSION: CTS may present acutely without a clinically identifiable cause. US complements electrodiagnostic studies and is particularly useful when electrodiagnostic tests are non-diagnostic (due to absent compound muscle and sensory action potentials). US may also provide clues to the underlying cause.

Essential tremor amplitude modulation by median nerve stimulation.

Essential tremor is a common neurological disorder, characterised by involuntary shaking of a limb. Patients are usually treated using medications which have limited effects on tremor and may cause side-effects. Surgical therapies are effective in reducing essential tremor, however, the invasive nature of these therapies together with the high cost, greatly limit the number of patients benefiting from them. Non-invasive therapies have gained increasing traction to meet this clinical need. Here, we test a non-invasive and closed-loop electrical stimulation paradigm which tracks peripheral tremor and targets thalamic afferents to modulate the central oscillators underlying tremor. To this end, 9 patients had electrical stimulation delivered to the median nerve locked to different phases of tremor. Peripheral stimulation induced a subtle but significant modulation in five out of nine patients-this modulation consisted mainly of amplification rather than suppression of tremor amplitude. Modulatory effects of stimulation were more pronounced when patient's tremor was spontaneously weaker at stimulation onset, when significant modulation became more frequent amongst subjects. This data suggests that for selected individuals, a more sophisticated control policy entailing an online estimate of both tremor phase and amplitude, should be considered in further explorations of the treatment potential of tremor phase-locked peripheral stimulation.

Comparison of short- and long-axis nerve hydrodissection for carpal tunnel syndrome: A prospective randomized, single-blind trial.

Background: This study is to compare the efficacy of short-axis hydrodissection with long-axis hydrodissection for patients with mild-to-moderate carpal tunnel syndrome (CTS). Methods: Forty-seven patients with mild-to-moderate CTS were enrolled in a prospective, randomized, single-blinded, controlled trial (6 months follow-up). With ultrasound guidance, patients in both groups (short-axis or long-axis groups) were injected with normal saline (5 mL per session). Assessments were performed before and 2 weeks after the injection, as well as at 1, 3, and 6 months post-intervention. The primary outcome measure was the Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) score and secondary outcomes included the cross-sectional area of the median nerve and electrophysiological studies. Results: Forty-four patients (21 wrists in the short-axis group and 23 wrists in the long-axis group) completed the study. Compared with the baseline, both groups showed improved BCTQ and cross-sectional area at all follow-up assessments (p<0.05). The short-axis group was not more effective except significant improvements in BCTQ-severity and BCTQ-function 1 month post-injection compared to the long-axis group (p = 0.031 and p = 0.023, respectively). Conclusions: Both short- and long-axis hydrodissection were effective for patients with mild-to-moderate CTS and the short-axis approach was not more effective than long-axis injection. Further studies with larger sample sizes, multiple injections, and larger injection volume are encouraged in the future.

Enlarged high frequency oscillations of the median nerve somatosensory evoked potential and survival in amyotrophic lateral sclerosis.

OBJECTIVE: A large N20 and P25 of the median nerve somatosensory evoked potential (SEP) predicts short survival in amyotrophic lateral sclerosis (ALS). We investigated whether high frequency oscillations (HFOs) over N20 are enlarged and associated with survival in ALS. METHODS: A total of 145 patients with ALS and 57 healthy subjects were studied. We recorded the median nerve SEP and measured the onset-to-peak amplitude of N20 (N20o-p), and peak-to-peak amplitude between N20 and P25 (N20p-P25p). We obtained early and late HFO potentials by filtering SEP between 500 and 1 kHz, and measured the peak-to-peak amplitude. We followed up patients until endpoints (death or tracheostomy) and analyzed the relationship between SEP or HFO amplitudes and survival using a Cox analysis. RESULTS: Patients showed larger N20o-p, N20p-P25p, and early and late HFO amplitudes than the control values. N20p-P25p was associated with survival periods (p = 0.0004), while early and late HFO amplitudes showed no significant association with survival (p = 0.4307, and p = 0.6858, respectively). CONCLUSIONS: The HFO amplitude in ALS is increased, but does not predict survival. SIGNIFICANCE: The enlarged HFOs in ALS might be a compensatory phenomenon to the hyperexcitability of the sensory cortex pyramidal neurons.

Cortical somatosensory processing after botulinum toxin therapy in post-stroke spasticity.

ABSTRACT: In dystonic and spastic movement disorders, abnormalities of motor control and somatosensory processing as well as cortical modulations associated with clinical improvement after botulinum toxin A (BoNT-A) treatment have been reported, but electrophysiological evidence remains controversial. In the present observational study, we aimed to uncover central correlates of post-stroke spasticity (PSS) and BoNT-A-related changes in the sensorimotor cortex by investigating the cortical components of somatosensory evoked potentials (SEPs). Thirty-one chronic stroke patients with PSS of the upper limb were treated with BoNT-A application into the affected muscles and physiotherapy. Clinical and electrophysiological evaluations were performed just before BoNT-A application (W0), then 4 weeks (W4) and 11 weeks (W11) later. PSS was evaluated with the modified Ashworth scale (MAS). Median nerve SEPs were examined in both upper limbs with subsequent statistical analysis of the peak-to-peak amplitudes of precentral P22/N30 and postcentral N20/P23 components. At baseline (W0), postcentral SEPs were significantly lower over the affected cortex. At follow up, cortical SEPs did not show any significant changes attributable to BoNT-A and/or physiotherapy, despite clear clinical improvement. Our results imply that conventional SEPs are of limited value in evaluating cortical changes after BoNT-A treatment and further studies are needed to elucidate its central actions.

Automated Segmentation of the Median Nerve in the Carpal Tunnel using U-Net.

Nerve area and motion in carpal tunnel syndrome (CTS) are currently under investigation in terms of prognostic potential. Therefore, there is increasing interest in non-invasive measurement of the nerve using ultrasound. Manual segmentation is time consuming and subject to inter-rater variation, providing an opportunity for automation. Dynamic ultrasound images (n = 5560) of carpal tunnels from 99 clinically diagnosed CTS patients were used to train a U-Net-shaped neural network. The best results from the U-Net were achieved with a location primer as initial region of interest for the segmentations during finger flexion (Dice coefficient = 0.88). This is comparable to the manual Dice measure of 0.92 and higher than the resulting automated Dice measure of wrist flexion (0.81). Although there is a dependency on image quality, a trained U-Net can reliably be used in the assessment of ultrasound-acquired median nerve size and mobility, considerably decreasing manual effort.

Utility of Preoperative Electrodiagnosis Together with Peripheral Nerve High-Resolution Ultrasound: A Complex Case Report of Neurofibromatosis Type I.

Our case report underscores the importance of electroneuromyography (ENMG) combined with peripheral nerve high-resolution ultrasound (HRUS) in the evaluation of neurofibromatosis type 1 (NF1). A 49-year-old woman affected by NF1 came to our attention because of new-onset left arm weakness and atrophy. Debulking of a cervicothoracic C7-T1 neurofibroma had been performed 8 years earlier. On current admission, magnetic resonance imaging disclosed increased lesion volume that was thought to cause the neurologic deficits by compressing the C8 root. Findings from intraoperative neurophysiologic monitoring during repeat debulking suggested that C8 root integrity had been compromised during the first operation and that the new-onset symptoms probably stemmed from peripheral nervous system damage distal to the cervical roots. Postoperative ENMG showed chronic denervation signs in the muscles innervated by C7-C8-T1 roots, moderate carpal tunnel syndrome (CTS), and ulnar nerve conduction block at the elbow. HRUS confirmed the CTS and revealed multiple neurofibromas involving the distal tract of the radial, ulnar, and median nerves. Surgical debulking was considered unnecessary in this case. ENMG combined with nerve and plexus HRUS evaluation may help identify the cause of neurologic deficits and choose the best surgical option in such complex clinical conditions as NF1.

[A case of Fisher syndrome presented by rapidly progressing bilateral palatoplegia after cytomegalovirus infection].

A 35-year-old male developed sensory abnormality of peripheral limbs and oral cavity after prior infection with diarrhea and cold symptoms. Hyperrhinolalia, nasopharyngeal reflux, double vision, and wobbling in walking rapidly progressed. Neurological examination revealed palatoplegia, omnidirectional ophthalmoplegia, hyperreflexia, sensory disturbance of extremities, and truncal and limb ataxia due to decreased deep sensation. A peripheral nerve conduction study found a slight decrease in sensory nerve action potential of the median nerve and a decrease in F wave frequency of the median nerve. Serum IgM-CMV antibody was positive on admission. After IVIg therapy, palatoplegia and ataxia markedly improved. In this case, GalNAc-GD1a and GM2 antibodies, which are often detected after CMV infection, were positive in addition to the GT1a and GQ1b antibodies, and it was assumed that these findings were associated with the palatoplegia, which is included in cranial nerve palsy. Pathophysiologically, the present case is considered to be an overlap with acute oropharyngeal palsy (AOP), which is a rare subtype of Guillain-Barre syndrome, and Fisher syndrome (FS). The clinical aspects of the present case suggest a continuous spectrum between AOP and FS.

Applicability of High-Frequency Ultrasound to the Early Diagnosis of Diabetic Peripheral Neuropathy.

This study investigated the applicability of high-frequency ultrasound (HFU) to the early diagnosis of diabetic peripheral neuropathy (DPN). Patients with type 2 diabetes (N = 60) were divided into diabetic nonperipheral neuropathy and DPN groups (group A and group B, respectively; n = 30 each) based on electroneurophysiologic findings. Additionally, 30 nondiabetic patients were included as the healthy control group (group C). We calculated the cross-sectional area (CSA) of the median nerve (MN) of the right upper limb at 7 different sites (MN1-7) based on measured width (W) and thickness (T). Ultrasound imaging characteristics of the MN including internal echo, internal structure, boundary, epineurium, and blood flow were recorded. The 90 subjects (51 male and 39 female) had an average age of 56.09 ± 12.66 years. W, T, and CSA of the MN were increased in group A compared to group C (with significant differences at MN1, MN4, and MN7 (P < 0.05)) and in group B compared to group C (with significant differences at all 7 levels, especially MN6 and MN7 (P < 0.05)). Receiver operating characteristic curve analysis showed that CSA at the MN7 level had the highest diagnostic accuracy for DPN in group B, with a threshold value of 12.42 mm2. Ultrasound examination revealed that the MN had lost the internal sieve mesh structure and showed reduced echo, a partial blood flow signal, and thickened epineurium in patients with DPN; these findings were particularly obvious at MN6 and MN7, corresponding to the carpal tunnel. CSA was positively correlated with motor latency and F wave average latency and negatively correlated with motor conduction velocity, motor amplitude, and sensory conduction velocity in group B. Thus, HFU may be useful for the early diagnosis of DPN, which can improve clinical outcomes.

Bi-allelic loss of function variants in COX20 gene cause autosomal recessive sensory neuronopathy.

Sensory neuronopathies are a rare and distinct subgroup of peripheral neuropathies, characterized by degeneration of the dorsal root ganglia neurons. About 50% of sensory neuronopathies are idiopathic and genetic causes remain to be clarified. Through a combination of homozygosity mapping and whole exome sequencing, we linked an autosomal recessive sensory neuronopathy to pathogenic variants in the COX20 gene. We identified eight unrelated families from the eastern Chinese population carrying a founder variant c.41A>G (p.Lys14Arg) within COX20 in either a homozygous or compound heterozygous state. All patients displayed sensory ataxia with a decrease in non-length-dependent sensory potentials. COX20 encodes a key transmembrane protein implicated in the assembly of mitochondrial complex IV. We showed that COX20 variants lead to reduction of COX20 protein in patient's fibroblasts and transfected cell lines, consistent with a loss-of-function mechanism. Knockdown of COX20 expression in ND7/23 sensory neuron cells resulted in complex IV deficiency and perturbed assembly of complex IV, which subsequently compromised cell spare respiratory capacity and reduced cell proliferation under metabolic stress. Consistent with mitochondrial dysfunction in knockdown cells, reduced complex IV assembly, enzyme activity and oxygen consumption rate were also found in patients' fibroblasts. We speculated that the mechanism of COX20 was similar to other causative genes (e.g. SURF1, COX6A1, COA3 and SCO2) for peripheral neuropathies, all of which are functionally important in the structure and assembly of complex IV. Our study identifies a novel causative gene for the autosomal recessive sensory neuronopathy, whose vital function in complex IV and high expression in the proprioceptive sensory neuron further underlines loss of COX20 contributing to mitochondrial bioenergetic dysfunction as a mechanism in peripheral sensory neuron disease.

Median nerve swelling is an independent risk factor of carpal tunnel syndrome in chronic hemodialysis patients.

Carpal tunnel syndrome (CTS) has a wide variety of underlying causes and occurs in association with dialysis. Early diagnosis is essential to prevent permanent nerve damage and functional sequelae. We evaluated the association between CTS and cross-sectional area (CSA) of the median nerve in chronic hemodialysis (HD) patients. Patients with end-stage renal disease on maintenance HD via arteriovenous fistula were enrolled. We divided 43 patients into two groups; patients diagnosed with CTS (n = 19) and patients without CTS (n = 24). The median nerve CSA was measured at the wrist (CSA-W) and forearm (CSA-F) by ultrasonography. Median nerve swelling was assessed by the wrist-to-forearm ratio (WFR). There were no significant differences in the underlying causes of chronic kidney disease and adequacy of dialysis between the two groups (p = NS). The patients with CTS showed significantly higher WFR than the patients without CTS (p = 0.001). Univariate Cox regression analysis revealed that WFR >1.25 (odds ratio, 6.30; 95% confidence interval, 1.44-27.45; p = 0.014) was associated with CTS in HD patients. The factors traditionally associated with CTS such as age, sex, diabetes, vintage of HD, ß2-MG, intact PTH, and Kt/V were not associated with CTS. After adjustment for age and sex, we found a strong correlation between CTS and the WFR >1.25 (odds ratio, 10.8; 95% confidence interval, 1.85-62.4; p = 0.008). High WFR was associated with the development of CTS, and median nerve swelling was an independent risk factor of CTS in chronic HD patients.

Prolonged median distal sensory nerve action potential duration in carpal tunnel syndrome.

OBJECTIVE: Routine nerve conduction study (NCS) parameters are less sensitive in the early stage of carpal tunnel syndrome (CTS). Recently, some studies have shown that prolonged distal sensory nerve action potential (DSNAP) duration may be a more sensitive technique for the diagnosis of demyelinating peripheral neuropathies. We aimed to evaluate the sensitivity of median DSNAP duration in patients with CTS. METHODS: DSNAP duration and routine NCS data of the median nerve were retrospectively collected in 173 CTS patients, 73 controls, and 78 cervical radiculopathy patients. RESULTS: Prolonged median DSNAP durations were found in 22 patients (22/35, 63%) and 36 patients (36/54, 67%) in the minimal and mild CTS groups respectively, which was more sensitive than routine NCS parameters. The percentage of patients demonstrating abnormalities in median NCS was significantly increased from 80% to 92% with the addition of DSNAP duration. CONCLUSION: Our results demonstrate the electrodiagnostic value of median DSNAP duration for the diagnosis of CTS, especially in early cases.

Variance in the pathophysiological impact of the hemizygosity of gamma-aminobutyric acid type A receptor subunit genes between Prader-Willi syndrome and Angelman syndrome.

INTRODUCTION: Angelman syndrome (AS) and Prader-Willi syndrome (PWS) are neurodevelopmental disorders caused by loss of function of maternally expressed UBE3A and paternally expressed contiguous genes on chromosome 15q11-13, respectively. A majority of these syndromes suffer from a large deletion of the relevant chromosome (AS Del or PWS Del), which includes biallelically expressed gamma-aminobutyric acid type A receptor subunit (GABAaR) genes, while remaining individuals present without the deletion (AS non-Del or PWS non-Del). We previously reported that AS Del, but not AS non-Del individuals, show aberrantly desynchronized somatosensory-evoked magnetic fields (SEFs) and speculated that it might reflect GABAergic dysfunction due to the hemizygosity of GABAaR genes. To verify its pathophysiological impact on PWS and AS, we analyzed the SEFs of PWS individuals. METHOD: SEFs were recorded from eight PWS Del and two PWS non-Del individuals. The latency and strength of the first peak (N1m) were compared with those of AS Del/non-Del individuals and controls, most of which were obtained earlier. RESULTS: In contrast to AS, both PWS Del and PWS non-Del showed normal SEF waveforms. Desynchronized response with delayed N1m peak latency was exclusively indicated in AS Del. N1m strength was statistically higher in AS Del and AS non-Del, but not in PWS Del and PWS non-Del. CONCLUSIONS: Our results indicate that the pathophysiological impact of the hemizygosity of GABAaR genes is lower in PWS than AS. UBE3A deficiency and the hemizygosity of GABAaR genes could synergistically deteriorate neuronal function, resulting in aberrant SEFs in AS Del.