Y.L. Lo

Clinical and immunological spectrum of the Miller Fisher syndrome.

The Miller Fisher syndrome (MFS), characterized by ataxia, areflexia, and ophthalmoplegia, was first recognized as a distinct clinical entity in 1956. MFS is mostly an acute, self‐limiting condition, but there is anecdotal evidence of benefit with immunotherapy. Pathological data remain scarce. MFS can be associated with infectious, autoimmune, and neoplastic disorders. Radiological findings have suggested both central and peripheral involvement. The anti‐GQ1b IgG antibody titer is most commonly elevated in MFS, but may also be increased in Guillain–Barré syndrome (GBS) and Bickerstaffs brainstem encephalitis (BBE). Molecular mimicry, particularly in relation to antecedent Campylobacter jejuni and Hemophilus influenzae infections, is likely the predominant pathogenic mechanism, but the roles of other biological factors remain to be established. Recent studies have demonstrated the presence of neuromuscular transmission defects in association with anti‐GQ1b IgG antibody, both in vitro and in vivo. Collective findings from clinical, radiological, immunological, and electrophysiological techniques have helped to define MFS, GBS, and BBE as major disorders within the proposed spectrum of anti‐GQ1b IgG antibody syndrome. Muscle Nerve, 2007

Recurrent jaw dislocation after botulinum toxin treatment for sialorrhoea in amyotrophic lateral sclerosis

Botulinum toxin (BTX) has been used successfully to treat various movement disorders, and is increasingly used for many other medical conditions. Sialorrhoea is a disabling symptom in many neurological patients including those with Parkinsons disease, stroke and amyotrophic lateral sclerosis (ALS). BTX has recently been shown to be effective for treating sialorrhoea. We report an ALS patient who developed recurrent jaw dislocation following BTX treatment for sialorrhoea to highlight the observation that intraparotid BTX may be complicated by jaw dislocations in some at-risk ALS patients. Clinicians using BTX to treat sialorrhoea in ALS need to be aware of this potentially serious complication.

Intraoperative motor-evoked potential monitoring in scoliosis surgery: comparison of desflurane/nitrous oxide with propofol total intravenous anesthetic regimens.

Study Design A prospective, randomized study in a large general hospital setting. Background During spinal surgery, monitoring motor-evoked potentials (MEPs) is a means of assessing the intraoperative integrity of corticospinal pathways. However, MEPs are known to be sensitive to the effects of anesthetic agents. Objective To compare the use of desflurane or total intravenous anesthetic regimens (TIVA) with multipulse cortical stimulation for intraoperative monitoring (IOM). Methods Twenty consecutive patients (10 in each arm) undergoing scoliosis correction surgery were randomly assigned to 2 equal groups receiving desflurane or TIVA. Inhalational anesthesia was maintained using 66% nitrous oxide in oxygen and a mean end-tidal desflurane concentration of 3.4%. For TIVA, continuous intravenous infusion of propofol was used. For analgesia, fentanyl and morphine were given when required for both groups. Cortical stimulation was achieved with 2 bipolar direct current stimulators connected in parallel by jumper cables. Five equivalent pulses 0.5 ms in duration at 4 ms intervals were delivered at C1C2 positions. MEP recordings were made in the abductor hallucis (AH) and tibialis anterior (TA) with needle electrodes. Results Reproducible MEPs were obtained throughout the operation in all 20 cases, with up to 80 mA per stimulator. Before insertion of pedicle screws, mean MEP amplitudes (SD) obtained were 85 (19) and 21.7 (10.8) mV for AH and TA, respectively, using desflurane. With TIVA, amplitudes were 56.7 (28.4) and 59.1 (24.5) mV, respectively. Both muscle MEP amplitudes were significantly different using different anesthetic regimens (P<0.05 for all). AH MEP amplitudes obtained with desflurane were significantly larger than TA amplitudes (P<0.0001). No complications were reported intraoperatively and postoperatively. Conclusions This is the first study comparing the use of desflurane and TIVA showing that both anesthetic regimens allowed successful intraoperative monitoring useage throughout the procedures. For MEP recording, the AH was the preferred muscle with a desflurane anesthetic regimen.

The role of clinical neurophysiology in bioterrorism

Chemical and biological agents have been used as weapons of mass destruction for a long time and presents as a serious threat to mankind. They have been used in many great wars and terrorist attacks with devastating results. The knowledge about these weapons of mass destruction is crucial to health care providers. Early recognition of the clinical characteristics of poisoning as a result of these chemical and biological agents is important to initiate appropriate therapy and minimizing casualties. Neurophysiological investigations when integrated with clinical features are helpful in early identification of some of these agents, especially when serological confirmation is not rapidly available. In this review, we have focused on chemical and biological weapons, which affect the nervous system and the role of clinical neurophysiology in such conditions.

Is hypertension associated with hemifacial spasm

Hemifacial spasm (HFS) is characterized by intermittent twitching of the muscles innervated by the ipsilateral facial nerve.1 Reports of normalization of blood pressure after vascular decompression in hypertensive patients suggest an association of hypertension with brainstem compression.2 A recent multicenter case–control study demonstrated a significantly higher prevalence of hypertension in white patients with HFS.3 The cause and effect of hypertension in HFS might have an impact on the management of HFS. Using case–control methodology, we examined the association of hypertension and HFS among HFS patients in our population and investigated differences in neurovascular contact (NVC) of the root exit zone (REZ) of the seventh cranial nerve in HFS patients with and without hypertension using high-resolution MRI/MR angiography (MRA). Methods. Consecutive HFS patients (117) from the movement disorder clinic and controls (245) without HFS seen in the general outpatient clinic for conditions unrelated to hypertension were included in the study. For every HFS patient, we selected two controls of similar age, sex, ethnicity, and body mass index (BMI). A history of hypertension was not an exclusion criterion. All HFS patients were offered brain MRI/MRA as part of the evaluation. We defined hypertension by World Health Organization classification criteria,4 which we also used in our recent National Health Survey (http//www.moh.gov.sg): systolic pressure 140 mm Hg or diastolic pressure 90 mm Hg, or both. Blood pressure was measured using standardized methods3-5 over two to three visits for a period of months as recommended for the diagnosis of hypertension. The imaging comprised three-dimensional time-offlight MRA (TR35, TE6, FA20, 1 nex,192 512 matrix, 1.0-mm partitions) and constructive interference at steady-state sequences (TR12, TE6, FA70, 2 nex, 230 512 matrix, 0.7-mm partitions). A neuroradiologist blinded to the side of HFS interpreted the images. NVC of the seventh cranial nerve was defined as the presence of vascular contact, compression of its REZ, or both. The following data of HFS patients and controls were analyzed: age, sex, duration of HFS, side of HFS, duration of hypertension, associated medical conditions, and MRI/MRA findings. The history of the duration of hemifacial spasm and a history of hypertension were obtained from the patients and corroborated by family members or physicians. Results. The demographics of the study subjects are shown in the table. The mean duration of HFS was 3.9 3.7 (standard deviation [SD]) years (range 0.1 to 20). The mean duration of hypertension in HFS patients and controls was 7.1 8.3 (SD) years (range 0.1 to 30) and 7.2 6.5 (SD) years (range 0.5 to 40). There was no significant difference between the prevalence of hypertension in HFS and controls (see the table). We used multivariate logistic regression analysis with step-wise variable selection for the following variables for both patients and controls: hypertension, diabetes mellitus, renal impairment, ischemic heart disease, cerebrovascular accident, smoking, and alcohol. We did not find significant confounding variables for the association of hypertension with HFS. MRI/MRA was performed in 96 (82.0%) of the 117 HFS patients. NVC of seventh cranial nerve on the side of HFS was found in 90 (93.8%) of patients who underwent MRI/MRA examination. Fourteen of them (14.6%) had NVC bilaterally. The most common offending vessel was the anterior inferior cerebellar artery. The actual vessel could not be identified in 2 of 96 (2.1%). NVC of the seventh cranial nerve was found in 39 of 41 (95.1%) and 51 of 55 (92.7%) in hypertensive and nonhypertensive HFS. Discussion. Although the prevalence of hypertension in HFS was higher (42.7% versus 39.1%) compared to controls matched for age, sex, and BMI, the difference was not significant (see the table). Stratifying the patients and controls by age groups also did not reveal any significant difference of hypertension between the two groups. Similar conclusions were found when we compared the findings with our population controls (National Health Population Survey, 1998). A large difference in the hypertension prevalence (40% to 50%) between HFS and controls would be necessary to impact our clinical management of the majority of HFS patients. As there was probably a selection bias for the more severe HFS patients in the movement disorder clinic, a higher than expected prevalence of hypertension in HFS would have been observed. However, our findings suggested that hypertension was not a major risk factor for HFS in our population. Unlike previous studies,3,5,6 we used controls matched for age, sex, and BMI, and our patients were investigated with highresolution MRI/MRA techniques highly sensitive for NVC in HFS. The availability of population control data based on similar methodology has helped to increase the power of analysis. We did not have imaging data in our study controls and could not investigate the association of NVC of the REZ of the seventh nerve or the ventrolateral medulla with hypertension. However, in a previous MRI/MRA study, NVC of the seventh cranial nerve in our control population was 25%,7 much lower than the 95.1% and 92.7% in our hypertensive and nonhypertensive HFS patients in this study. This suggests that NVC of the REZ of the seventh cranial nerve is unlikely to be associated with hypertension. Our results suggest that there may be etiologic differences among the races. It is possible that anatomic differences in the

Acute ophthalmoparesis in the anti-GQ1b antibody syndrome: electrophysiological evidence of neuromuscular transmission defect in the orbicularis oculi.

Objective: To prospectively study anti-GQ1b antibody positive cases of acute ophthalmoparesis (AO) clinically and electrophysiologically. Methods: Nine consecutive cases presenting with predominantly acute ophthalmoplegia were assessed clinically and had stimulated single fibre electromyography (SFEMG) of the orbicularis oculi at presentation. All had magnetic resonance imaging brain scans and anti-GQ1b antibody titres determined. Results: Four cases had elevated anti-GQ1b antibody titres and abnormal SFEMG studies, which improved in tandem with clinical recovery over three months. Five other anti-GQ1b antibody negative cases were diagnosed as diabetic related cranial neuropathy, idiopathic cranial neuropathy, ocular myasthenia gravis, and Tolosa-Hunt syndrome. All five cases showed complete recovery over a three month period. Conclusions: This study demonstrated electrophysiologically the dynamic improvement of neuromuscular transmission of anti-GQ1b antibody positive cases of AO, in tandem with clinical recovery. SFEMG is of value in differentiating weakness due to neuromuscular transmission defect from neuropathy in these clinical situations.

Statin therapy and small fibre neuropathy: a serial electrophysiological study

We describe three patients who developed small fibre neuropathy after 1 month of statin therapy with clinical resolution upon prompt drug withdrawal. All patients showed abnormal sympathetic skin responses (SSR) in comparison with controls. SSRs returned to normal in tandem with clinical improvement. One patient redeveloped small and large fibre neuropathy when the similar drug was readministered. The SSR is of value in the electrophysiological assessment and follow-up of statin-related small fibre neuropathy.

Three-dimensional MR volumetric analysis of the posterior fossa CSF space in hemifacial spasm

Background: We hypothesize that a smaller posterior fossa (PF) CSF space may be a risk factor for hemifacial spasm (HFS). Objective: We conducted a case-control 3-dimensional magnetic resonance (MR) volumetric study in patients with HFS and determined the clinical predictive factors of PF CSF volume. Methods: Patients with clinically diagnosed HFS and controls matched for age, sex, race, and hypertension underwent MRI/magnetic resonance angiography examination. The PF CSF space was segmented and quantified on a heavily T2-weighted high-resolution 3-dimensional MR volume slab, centered over the porus acusticus. Results: Eighty-two study subjects (41 patients and 41 controls) were included. The mean PF CSF volume in patients with HFS and controls was 17,303.0 ± 3,900.0 vs 19,216.0 ± 3,912.0 mm3. The mean volume in patients with HFS was 11.4% smaller than in controls (p = 0.015). Analysis of differences between individually matched pairs and controls also revealed that PF CSF for controls was larger than that for patients with HFS (p = 0.007). A multivariate linear regression analysis revealed that a small PF CSF volume was associated with HFS (p = 0.01). Decreasing age (p = 0.001) and female gender (p < 0.0005), but not hypertension (p = 0.892), were also found to be predictors of a low PF CSF volume. Conclusions: Our results showed that the posterior fossa (PF) CSF volume was lower in patients with HFS compared with matched controls. HFS, female gender, and younger age were associated with smaller PF CSF volume. These observations could explain the strong female preponderance in both clinic- and population-based epidemiologic studies.

Presynaptic neuromuscular transmission defect in the Miller Fisher syndrome

The Miller Fisher syndrome (MFS) is associated with elevated anti-GQ1b antibodies.1 The pathophysiology of MFS involves immunologically mediated central and peripheral processes.2 In vitro studies of MFS have demonstrated anti-GQ1b-mediated presynaptic damage at the neuromuscular junction.3 This mechanism may be responsible for some of its clinical manifestations. Repetitive nerve stimulation (RNS) is a validated electrophysiologic technique for assessing neuromuscular transmission.4 In this study, we present serial RNS data on patients with MFS, in relation to their clinical course. Over a 3-year period, we prospectively evaluated six consecutive previously healthy patients presenting with MFS. The patients presented with the classic clinical triad (ataxia, areflexia, and ophthalmoplegia) of MFS, and none was weak. All patients had a complete neurologic examination as well as routine nerve conduction studies. Anti-Gq1b assays5 were performed during hospital admission. RNS of the ulnar nerve was performed with right abductor digiti minimi recording.4 RNS was performed at the following frequencies in random order: 3 Hz at rest, 3 Hz post exercise, 20 Hz, and 50 Hz. Exercise consisted of 20 seconds of maximal muscle activation. Each …

Cervical disc prolapse with cord compression presenting with choreoathetosis and dystonia

Movement disorders from spinal cord disease are rare and can be caused by underlying neoplasm, inflammation, demyelination, or trauma.1-4⇓⇓⇓ Cervical radiculopathy caused by disc herniation or cervical spondylosis is common and important to recognize because it may improve after decompression surgery. We describe a patient with cervical disc prolapse presenting with choreoathetosis and dystonia. A previously well 62-year-old Chinese woman presented with involuntary movements of her upper extremities of 3-month duration. She observed that her fingers would wriggle on their own and her arms would move involuntarily. These movements were much worse during action than rest. She reported no premonition or any urge before these movements, and did not feel any relief afterwards. The movements were aggravated by stress, agitation, or anxiety, and were relieved by rest and sleep. She also noted that her fingers (particularly the index and middle fingers) would intermittently go into spasms, with involuntary flexion at the metacarpal-phalangeal joints; these spasms were relieved by putting her fingers in contact with other body parts. In addition, she had concurrent “tingling” sensations of the fingertips of both hands (right more severely affected). There were no abnormal movements involving the oro-facial-buccal region or lower extremities. She had no urinary or bowel complaints. There was no history of exposure to neuroleptic medications, severe head trauma, or dementia. No relatives …