Yee-Cheun Chan

Electroencephalographic changes and seizures in familial hemiplegic migraine patients with the CACNA1A gene S218L mutation.

The S218L CACNA1A mutation has been previously described in two families with familial hemiplegic migraine. We present three siblings with the mutation with the novel association of childhood seizures, and highlight the dynamic changes seen on electroencephalography during hemiplegic migraine attacks. Depressed activity contralateral to the hemiparesis was seen on electroencephalography during acute hemiplegic migraine attacks, which may be due to changes to calcium channels caused by the S218L mutation. Both parents were asymptomatic and did not carry the S218L mutation in their blood. This suggests the presence of mosaicism in the transmitting parent.

Antibodies to single glycolipids and glycolipid complexes in Guillain-Barré syndrome subtypes

Objective: To comprehensively investigate the relationship between antibodies to single glycolipids and their complexes and Guillain-Barré syndrome subtypes and clinical features. Methods: In acute sera from 199 patients with Guillain-Barré syndrome, immunoglobulin G (IgG) antibodies to glycolipids and ganglioside complexes were tested using ELISA against individual antigens from single glycolipids including gangliosides (LM1, GM1, GM1b, GD1a, GalNAc-GD1a, GD1b, GT1a, GT1b, GQ1b) and a neutral glycolipid, asialo-GM1 (GA1), and antigens from the combination of 2 different glycolipids. Based on serial nerve conduction studies, the electrodiagnoses were as follows: 69 demyelinating subtype, 85 axonal subtypes, and 45 unclassified. Results: Significant associations were detected between acute motor axonal neuropathy subtype and IgG antibodies to GM1, GalNAc-GD1a, GA1, or LM1/GA1 complex. Reversible conduction failure was significantly associated with IgG antibodies to GM1, GalNAc-GD1a, GD1b, or complex of LM1/GA1. No significant association was demonstrated between acute inflammatory demyelinating polyneuropathy and any of the glycolipids or ganglioside complexes. Anti-ganglioside complex antibodies alone were detected in 7 patients (5 axonal subtype). Conclusions: The current study demonstrates that antibodies to single glycolipids and ganglioside complexes are associated with acute motor axonal neuropathy or acute motor conduction block neuropathy but not acute inflammatory demyelinating polyneuropathy. Classification of evidence: This study provides Class II evidence that antibodies to glycolipids are increased in patients with acute motor axonal neuropathy and acute motor conduction block neuropathy but not acute inflammatory demyelinating polyneuropathy.

Does measuring the median nerve at the carpal tunnel outlet improve ultrasound CTS diagnosis

INTRODUCTION Nerve conduction is often regarded as more sensitive than ultrasonography (US) for diagnosing carpal tunnel syndrome (CTS). The diagnostic value of US derives from median nerve enlargement occurring at both ends of the carpal tunnel resulting in a dumbbell-like swelling from carpal tunnel pressure. An important reason for the inferior sensitivity of US may be because measurements are restricted to the carpal tunnel inlet. We investigate the value of including median nerve enlargement at the carpal tunnel outlet for diagnosing CTS. METHODS Retrospective cohort study of nerve conduction verified CTS, determining sensitivity, specificity, and positive and negative predictive values of carpal tunnel inlet and outlet median nerve cross sectional area as determined by US for the diagnosis of CTS. Nerve conduction graded CTS severity. RESULTS 127 hands from 77 patients with CTS and 35 control healthy hands were assessed. US sensitivity for diagnosing CTS increased from 65% to 84% by including outlet enlargement of the median nerve. Specificity changed from 94% to 86%, positive predictive value from 98% to 96% and the negative predictive value from 43% to 60%. 25 hands out of the 127 from CTS patients showed enlargement restricted to the outlet and mainly occurred in moderate CTS. CONCLUSION In our population, the use of carpal tunnel outlet median nerve enlargement in addition to inlet median nerve size increases sensitivity for diagnosing CTS by 19%.

Non-demyelinating, reversible conduction failure in a case of pharyngeal–cervical–brachial weakness overlapped by Fisher syndrome

Pathophysiologically, Guillain-Barré syndrome is divided into demyelinating and axonal subtypes. Recent studies have shown that serial nerve conduction studies (NCSs) are required to differentiate a demyelination-remyelination pathophysiology from one with axonal nodal reversible conduction failure. Cases with an overlap of pharyngeal-cervical-brachial weakness and Fisher syndrome (PCB/FS) are uncommon; the NCS findings of such cases have not been well described and the evolution of the NCS findings has not been previously studied. We describe the clinical features and serial NCS findings of a patient with PCB/FS. The evolution of abnormalities in NCS reflected a clinical pattern of weakness that progressed from the top of the body and descended toward the legs, and terminated before reaching the legs. The amplitudes of motor and sensory potentials were decreased, as is consistent with acute motor-sensory axonal neuropathy. However, the amplitudes recovered without the appearance of dispersed potentials seen in remyelination, implicating the pathophysiology of nodal reversible conduction failure. Together with the electrophysiological evidence of the pathophysiology of nodal reversible conduction failure in previously reported PCB patients and FS patients, our case suggests that PCB, FS and PCB/FS fall in a continuous spectrum with axonal GBS subtypes.

Atypical Bickerstaff brainstem encephalitis: ataxic hypersomnolence without ophthalmoplegia

Objective Clinical and immunological evaluation of ‘incomplete’ Bickerstaff brainstem encephalitis (BBE). Methods We studied two patients with postinfectious brainstem syndromes who presented at National University Hospital Singapore. Laboratory work-up included measurement of antiganglioside antibodies. Results Both patients displayed hypersomnolence and cerebellar-like ataxia in the absence of external ophthalmoplegia and carried high serum titres of IgG anti-GQ1b antibodies, strongly indicative of BBE. Conclusions Ophthalmoplegia can be absent or incomplete in BBE, and the absence of this clinical feature should not exclude BBE from the clinicians’ differential. Such cases of incomplete BBE could be defined as ‘ataxic hypersomnolence without ophthalmoplegia’.

The value of comparing mortality of Guillain–Barré syndrome across different regions

OBJECTIVE To study the clinical profile of Guillain-Barré syndrome (GBS) patients who died in 4 Asian countries in order to understand factors underlying any variation in mortality. METHODS Retrospectively reviewed medical records of GBS patients who died in 7 hospitals from 4 Asian countries between 2001 and 2012. Baseline characteristics, timing and causes of death were recorded. RESULTS A total of 16 out of 261 GBS patients died. The overall mortality rate was 6%, with a range of 0 to 13%. The leading causes of death were respiratory infections, followed by myocardial infarction. The median age of our patients was 77 years. Half of the patients required mechanical ventilation and almost all had significant concomitant illnesses. A disproportionate number of patients in the Hong Kong cohort died (13%). Patients with advanced age, fewer antecedent respiratory infections and need for mechanical ventilation were at most risk. Most deaths occurred during the plateau phase of GBS and on the general ward after having initially received intensive care. CONCLUSIONS There is considerable variability in mortality of GBS among different Asian cohorts. Although the risks factors for mortality were similar to Western cohorts, the timing and site of death differed. This allows specific measures to be implemented to improve GBS care in countries with higher mortality.

Electrodiagnosis of reversible conduction failure in Guillain‐Barré syndrome

Introduction: In this study we propose electrodiagnostic criteria for early reversible conduction failure (ERCF) in axonal Guillain–Barré syndrome (GBS) and apply them to a cohort of GBS patients. Methods: Serial nerve conduction studies (NCS) were retrospectively analyzed in 82 GBS patients from 3 centers. The criteria for the presence of ERCF in a nerve were: (i) a 50% increase in amplitude of distal compound muscle action potentials or sensory nerve action potentials; or (ii) resolution of proximal motor conduction block with an accompanying decrease in distal latencies or compound muscle action potential duration or increase in conduction velocities. Results: Of 82 patients from 3 centers, 37 (45%) had ERCF, 21 (26%) had a contrasting evolution pattern, and 8 (10%) had both. Sixteen patients did not show an amplitude increase of at least 50%. Conclusion: Our proposed criteria identified a group of patients with a characteristic evolution of NCS abnormality that is consistent with ERCF. Muscle Nerve 56: 919–924, 2017

Serial electrophysiological studies in a Guillain-Barré subtype with bilateral facial neuropathy

OBJECTIVE Bifacial weakness with paraesthesias subtype of Guillain-Barré syndrome (GBS) is thought to be demyelinating in nature but the evolution of serial nerve conduction study (NCS) findings has not been studied. We retrospectively analyzed the changes on serial NCS of patients with bilateral facial neuropathy. METHODS We described the clinical features, serial blink reflex, facial nerve and limb NCS of such patients. RESULTS Five patients fulfilled our study criteria. Patients 1 and 2 were diagnosed clinically to have bilateral Bells palsy, patients 3 and 4 as bifacial GBS subtype and patient 5 as facial palsy associated with acute HIV infection. In all, the initial neurophysiological tests showed absent blink response and normal facial NCS. Patient 1s repeat tests were normal. Patient 2s repeat blink reflex showed mildly prolonged latency. Repeat blink reflex latency of patients 3, 4 and 5 were in the demyelinating range. Patient 3 also had prolonged facial nerve latency. Patients 3 and 4 had serial limb NCS showing progressively prolonged latency. CONCLUSION Serial NCS suggests that the bifacial GBS subtype is demyelinating in nature. SIGNIFICANCE This study provides further evidence for a bifacial subtype of GBS with a demyelinating pathophysiology.

Are ERM (ezrin/radixin/moesin) proteins targets for autoantibodies in demyelinating neuropathies?

Ezrin, radixin and moesin, which are strongly expressed in the Schwann cell microvilli, are putative targets for autoantibodies in acute or chronic inflammatory demyelinating polyneuropathy (AIDP or CIDP). An association between anti-moesin IgG antibodies and cytomegalovirus-related AIDP has been postulated. None of 41 AIDP patients, including 8 cytomegalovirus-related AIDP patients, and 23 CIDP had IgG or IgM antibodies to ezrin, radixin and moesin; whereas, one patient with cytomegalovirus-related AIDP had anti-ezrin IgM antibodies. Ezrin, radixin and moesin are unlikely targets for autoantibodies in AIDP and CIDP, and the association of anti-moesin antibodies with cytomegalovirus-related AIDP was not confirmed.

PF3.4 Combined Doppler and B-Mode Sonography in Carpal Tunnel Syndrome

Background: Guillain Barré syndrome (GBS) is an acute immunedmediated polyneuropathy often after an antecedent infection. There are at least four subtypes based on clinical and electrophysiological findings: acute inflammatory demyelinating polyneuropathy (AIDP), acute motor and sensory axonal neuropathy (AMSAN), acute motor axonal neuropathy (AMAN) and Miller-Fisher syndrome (MFS). We describe the spectrum of GBS seen in a Malaysian population. Methods: GBS patients seen between 1995 and 2008 at the University of Malaya Medical Centre, Kuala Lumpur were included. The UMMC is a tertiary neurological referral centre for the country. Demographic data, clinical presentation and electrophysiological findings were reported. Diagnosis of GBS and its classification was based on clinical findings and the electrophysiological criteria of Hadden et al (1998). Results: There were 86 patients, 55 (64%) males. Mean age was 37.6 years (2 81). Ethnic backgrounds were Chinese 37 (43%), Malay 24 (27.9%), Indian 22 (25.6%) and other races 3 (3.5 %). Based on the initial electrophysiological study, 50 (58.1%) were AIDP and 11 (12.8%) had axonal neuropathy. Of these, 7 were AMAN and 4 were AMSAN. A further 15 (17.4%) had indeterminate electrophysiological findings, one (1.2%) had inexcitable nerves and six (7%) normal findings. Ten (11.6%) patients had MFS, which 4 had indeterminate electrophysiological findings and six normal findings. The majority of our patients, 72 (83.7%) were from urban areas. Conclusions: Unlike the spectrum of GBS seen in other developing countries such as northern China and Mexico, the spectrum in a mainly urban Malaysian population suggests a predominance of AIDP rather than axonal forms of GBS. There is also a relatively high percentage of MFS in our population.