Utility of Sensory Nerve Conduction Study in Radiologically Positive Lumbosacral Plexopathy.

MRI is the most appropriate imaging method for visual evaluation of lumbosacral plexopathy (LSP) and a reference for comparing with nerve conduction study (NCS). Eight patients with clinical, electrophysiological, and lumbosacral plexus MRI findings suggestive of LSP were prospectively recruited. Saphenous nerve abnormalities were present in seven patients (88%), compared to three for the superficial fibular (38%), and three for the sural nerve (38%). MRI showed tumor, hematoma, abscess, contrast enhancement, or hyperintense signals on the T2-weighted sequences. The SN has the highest yield in MRI positive LSP and may be a vital adjunct for electrophysiological evaluation of LSP.

Parkinson's disease genome-wide association study-linked PARK16 variant is associated with a lower risk of cognitive impairment: A 4-year observational study.

BACKGROUND AND PURPOSE: A genome-wide association study-linked variant (PARK16 rs6679073) modulates the risk of Parkinson's disease (PD). We postulate that there may be differences in clinical characteristics between PARK16 rs6679073 carriers and noncarriers. In a prospective study, we investigate the clinical characteristics between PARK16 rs6679073 A allele carriers and noncarriers over 4 years. METHODS: A total of 204 PD patients, comprising 158 PARK16 rs6679073 A allele carriers and 46 noncarriers, were recruited. All patients underwent motor and nonmotor symptom and cognitive assessments yearly over 4 years. RESULTS: PARK16 rs6679073 carriers were less likely to have mild cognitive impairment (MCI) compared to noncarriers at both baseline (48.1% vs. 67.4%, p = 0.027) and 4-year follow-up (29.3% vs. 58.6%, p = 0.007). CONCLUSIONS: PD PARK16 rs6679073 carriers had significantly lower frequency of MCI in a 4-year follow-up study, suggesting that the variant may have a neuroprotective effect on cognitive functions.

Parkinson's disease GWAS-linked Park16 carriers show greater motor progression.

BACKGROUND: Data on the long-term motor outcomes of genome-wide association study (GWAS)-linked Parkinson disease (PD) carriers are useful for clinical management. OBJECTIVES: To characterise the association between GWAS-linked PARK16 gene variant and disease progression in PD over a 9-year time frame. METHODS: Over a 9-year period, carriers of PARK16 rs11240572 variant and non-carriers were followed up and evaluated using the modified Hoehn and Yahr (H&Y) staging scale and Unified Parkinson's Disease Rating Scale (UPDRS) part III. A longitudinal, linear mixed model was performed to compare the changes of H&Y staging scale, UPDRS motor score and UPDRS subscores between the two groups. RESULTS: A total of 156 patients (41 PARK16 carriers and 115 non-carriers) were evaluated and followed up for up to 9 years. Using longitudinal linear mixed model analysis, there was a greater rate of deterioration in the motor function as measured by the UPDRS scores compared with non-carriers after 5 years from the date of diagnosis (p=0.009). In addition, we demonstrated that PARK16 variant carriers had worse gait scores (p=0.043) and greater motor progression than non-carriers after 6 years based on the modified H&Y staging scale (p=0.040). CONCLUSIONS: In a 9-year longitudinal study, we demonstrated that PD PARK16 variant carriers exhibited greater motor progression after 5 years of disease compared with non-carriers, suggesting that GWAS-linked gene variants may influence disease progression over time. Closer monitoring and management of these higher risk patients can facilitate a better quality of life.

Immunotherapy for diabetic amyotrophy.

BACKGROUND: People with diabetes mellitus (DM) sometimes present with acute or subacute, progressive, asymmetrical pain and weakness of the proximal lower limb muscles. The various names for the condition include diabetic amyotrophy, diabetic lumbosacral radiculoplexus neuropathies, diabetic femoral neuropathy or Bruns-Garland syndrome. Some studies suggest that diabetic amyotrophy may be an immune-mediated inflammatory microvasculitis causing ischaemic damage of the nerves. Immunotherapies would therefore be expected to be beneficial. This is the second update of a review first published in 2009. OBJECTIVES: To review the evidence from randomised trials for the efficacy of any form of immunotherapy in the treatment of diabetic amyotrophy. SEARCH METHODS: On 5 September 2016 we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE and Embase. We also contacted authors of relevant publications and other experts to obtain additional references, unpublished trials, and ongoing trials. SELECTION CRITERIA: We intended to include all randomised and quasi-randomised trials of any immunotherapy in participants with the condition fulfilling all the following: diabetes mellitus as defined by internationally recognised criteria; acute or subacute onset of pain and lower motor neuron weakness involving predominantly the proximal muscles of the lower limbs; weakness that is not confined to one nerve or nerve root distribution; and exclusion of other causes of lumbosacral radiculopathies and plexopathy. DATA COLLECTION AND ANALYSIS: Two authors independently examined all references retrieved by the search to select those meeting the inclusion criteria. MAIN RESULTS: We found only one completed placebo-controlled trial (N = 75) using intravenous methylprednisolone in diabetic amyotrophy (Dyck 2006). The results have not been fully published and were not available for analysis. The risk of bias was unclear because there was too little information to make a judgement, but we considered the trial at high risk of selective reporting. The published abstract did not report adverse events. We found no additional trials when the searches were updated in September 2016. AUTHORS' CONCLUSIONS: There is presently no evidence from randomised trials to support a positive or negative effect of any immunotherapy in the treatment in diabetic amyotrophy.

Migraine with Multiple Sensory Auras.

Migraine auras are typically visual in nature but can manifest as disturbances in somatosensory, auditory, and olfactory senses. Reports of multiple sensory auras are rare in the literature, but their existence may offer novel insights into the pathogenesis of this highly common yet complex neurological condition. Here we report a case of multiple sensory auras involving somatosensory, auditory, and olfactory disturbances in a patient with migraine without visual manifestations. A 45-year-old woman with a 20-year history of migrainous headaches presented with complaints of rightsided facial and hand numbness and paraesthesia. In addition to somatosensory symptoms, she eventually presented with tinnitus, cutaneous allodynia, and phantosmia, each of which was temporally associated with episodes of headache. No abnormalities were detected on NCS, EEG, MRI, and laboratory investigations. Her symptoms were managed by prophylactic medications and acupuncture. The theories of cortical spreading depression, cortical sensitization, and thalamocortical network involvement were discussed as possible explanations for sensory auras in migraine. This case report of migraine with multiple sensory auras spanning somatosensory, auditory, and olfactory modalities offers novel insights into the pathophysiology of migrainous auras.

Cortical Reorganization Is Associated with Surgical Decompression of Cervical Spondylotic Myelopathy.

BACKGROUND: Cervical spondylotic myelopathy (CSM) results in sensorimotor limb deficits, bladder, and bowel dysfunction, but mechanisms underlying motor plasticity changes before and after surgery are unclear. METHODS: We studied 24 patients who underwent decompression surgery and 15 healthy controls. Patients with mixed upper and lower limb dysfunction (Group A) and only lower limb dysfunction (Group B) were then analysed separately. RESULTS: The sum amplitude of motor evoked potentials sMEP (p < 0.01) and number of focal points where MEPs were elicited (N) (p < 0.001) were significantly larger in CSM patients compared with controls. For Group A (16 patients), sMEP (p < 0.01) and N (p < 0.001) showed similar findings. However, for Group B (8 patients), only N (p = 0.03) was significantly larger in patients than controls. Group A had significantly increased grip strength (p = 0.02) and reduced sMEP (p = 0.001) and N (p = 0.003) after surgery. Changes in sMEP (cMEP) significantly correlated inversely with improved feeding (p = 0.03) and stacking (p = 0.04) times as was the change in number of focal points (NDiff) with improved writing times (p = 0.03). Group B did not show significant reduction in sMEP or N after surgery, or significant correlation of cMEP or NDiff with all hand function tests. No significant differences in H reflex parameters obtained from the flexor carpi radialis, or central motor conduction time changes, were noted after surgery. DISCUSSION: Compensatory expansion of motor cortical representation occurs largely at cortical rather than spinal levels, with a tendency to normalization after surgery. These mirrored improvements in relevant tasks requiring utilization of intrinsic hand muscles.

Corpus Callosum-Mediated Interhemispheric Interactions in Cervical Spondylotic Myelopathy.

PURPOSE: The corpus callosum is crucial for interhemispheric interactions in the motor control of limb functions. Human and animal studies suggested spinal cord pathologies may induce cortical reorganization in sensorimotor areas. We investigate participation of the corpus callosum in executions of a simple motor task in patients with cervical spondylotic myelopathy (CSM) using transcranial magnetic stimulation. METHODS: Twenty patients with CSM with various MRI grades of severity of cord compression were compared with 19 normal controls. Ipsilateral silent period, contralateral silent period, central motor conduction time, and transcallosal conduction time (TCT) were determined. RESULTS: In both upper and lower limbs, TCTs were significantly increased for patients with CSM than normal controls ( p < 0.001 for all), without side-to-side differences. Ipsilateral silent period and contralateral silent period durations were significantly increased bilaterally for upper limbs in comparison to controls ( p < 0.01 for all), without side-to-side differences. There were no significant correlations of TCT with central motor conduction time nor severity of CSM for both upper and lower limbs ( p > 0.05 for all) bilaterally. CONCLUSIONS: Previous transcranial magnetic stimulation studies show increased motor cortex excitability in CSM; hence, increased TCTs observed bilaterally may be a compensatory mechanism for effective unidirectional and uniplanar execution of muscle activation in the distal limb muscles. Lack of correlation of TCTs with severity of CSM or central motor conduction time may be in keeping with a preexistent role of the corpus callosum as a predominantly inhibitory pathway for counteracting redundant movements resulting from increased motor cortex excitability occurring after spinal cord lesions.

Approach to headache disorders and the management of migraine: consensus guidelines from the Headache Society of Singapore, first edition (2023).

Headache disorders, particularly migraine, are one of the most common and disabling neurological disorders. There is a need for high-quality, accessible care for patients with headache disorders across all levels of the healthcare system in Singapore. The role of the Headache Society of Singapore is to increase awareness and advance the understanding of these disorders and to advocate for the needs of affected patients. In this first edition of local consensus guidelines, we focus on treatment approaches for headaches and provide consensus recommendations for the management of migraine in adults. The recommendations in these guidelines can be used as a practical tool in routine clinical practice by primary care physicians, neurologists and other healthcare professionals who have a common interest in headache disorders.

Immunotherapy for diabetic amyotrophy.

BACKGROUND: People with diabetes mellitus (DM) sometimes present with acute or subacute, progressive, asymmetrical pain and weakness of the proximal lower limb muscles. The various names for the condition include diabetic amyotrophy or diabetic lumbosacral radiculoplexus neuropathies. Some studies suggest that it may be due to immune-mediated inflammatory microvasculitis causing ischaemic damage of the nerves. Immunotherapies would therefore be expected to be beneficial. This is an update of a review first published in 2009. OBJECTIVES: We aimed to review the evidence from randomised trials for the efficacy of any form of immunotherapy in the treatment of diabetic amyotrophy. SEARCH METHODS: We searched the Cochrane Neuromuscular Disease Group Specialized Register (7 February 2012), CENTRAL (2012 Issue 1), MEDLINE (January 1966 to January 2012) and EMBASE (January 1980 to January 2012), and contacted authors of relevant publications and other experts to obtain additional references, unpublished trials, and ongoing trials. SELECTION CRITERIA: We intended to include all randomised and quasi-randomised trials of any immunotherapy in participants with the condition fulfilling all the following: diabetes mellitus as defined by internationally recognised criteria, acute or subacute onset of pain and lower motor neuron weakness involving predominantly the proximal muscles of the lower limbs, weakness that is not confined to one nerve or nerve root distribution and exclusion of other causes of lumbosacral radiculopathies and plexopathy. DATA COLLECTION AND ANALYSIS: Two authors independently examined all references retrieved by the search to select those meeting the inclusion criteria. MAIN RESULTS: We found only one completed controlled trial using intravenous methylprednisolone in diabetic amyotrophy (Dyck 2006). The results have not been fully published and were not available for analyses. We found no additional trials when the searches were updated in 2012. AUTHORS' CONCLUSIONS: There is presently no evidence from randomised trials to support any recommendation on the use of any immunotherapy treatment in diabetic amyotrophy.

Biomarker characterization of clinical subtypes of Parkinson Disease.

The biological underpinnings of the PD clusters remain unknown as the existing PD clusters lacks biomarker characterization. We try to identify clinical subtypes of Parkinson Disease (PD) in an Asian cohort and characterize them by comparing clinical assessments, genetic status and blood biochemical markers. A total of 206 PD patients were included from a multi-centre Asian cohort. Hierarchical clustering was performed to generate PD subtypes. Clinical and biological characterization of the subtypes were performed by comparing clinical assessments, allelic distributions of Asian related PD gene (SNCA, LRRK2, Park16, ITPKB, SV2C) and blood biochemical markers. Hierarchical clustering method identified three clusters: cluster A (severe subtype in motor, non-motor and cognitive domains), cluster B (intermediate subtype with cognitive impairment and mild non-motor symptoms) and cluster C (mild subtype and young age of onset). The three clusters had significantly different allele frequencies in two SNPs (Park16 rs6679073 A allele carriers in cluster A B C: 67%, 74%, 89%, p = 0.015; SV2C rs246814 T allele distribution: 7%, 12%, 25%, p = 0.026). Serum homocysteine (Hcy) and C-reactive protein (CRP) levels were also significantly different among three clusters (Mean levels of Hcy and CRP among cluster A B C were: 19.4 ± 4.2, 18.4 ± 5.7, 15.6 ± 5.6, adjusted p = 0.005; 2.5 ± 5.0, 1.5 ± 2.4, 0.9 ± 2.1, adjusted p < 0.0001, respectively). Of the 3 subtypes identified amongst early PD patients, the severe subtype was associated with significantly lower frequency of Park16 and SV2C alleles and higher levels of Hcy and CRP. These biomarkers may be useful to stratify PD subtypes and identify more severe subtypes.

Recurrent ipsilateral hemiparesis in a patient with both uncrossed corticospinal tracts and reorganization of cortical motor areas - An opportune visitation of the motor tracts.

We report the case of a patient who experienced recurrent ipsilateral hemiparesis in the setting of predominantly-uncrossed corticospinal tracts, with concomitant neuronal reorganization of the cortical motor maps, and the presence of aberrant interhemispheric connections. Their presence was supported by our results from diffusion tensor imaging tractography, functional magnetic resonance imaging, and transcranial magnetic stimulation. To our knowledge, this has never been reported before, and provides valuable insights into the mechanisms behind post-stroke motor recovery.

Prognostic factors of key outcomes for motor neuron disease in a multiracial Asian population.

BACKGROUND: Knowledge of prognostic factors related to the survival of Motor Neuron Diseases (MND) remains scarce in Southeast Asia. PURPOSE: To determine potential prognostic factors for survival, need for feeding and ventilation support in MND patients in a multi-racial Asian population. METHODS: One hundred and four MND patients from the Singapore General Hospital (SGH) between January 2004 and December 2017 were reviewed. All relevant clinical data, demographic information were collected. Kaplan-Meier and Cox regression model were performed to identify potential prognostic factors for crucial outcomes (survival, need for feeding support and ventilation support). RESULTS: Mean age of onset was 59.54 ± 10.91 years, Mean age of onset in Malays was significantly younger than that of other ethnic groups (Malay: 54.18 ± 12.95 years; Non-Malay: 60.39 ± 10.38 years, p = 0.035). Fifty six of the male and 33of the female were diagnosed with ALS (90.3% vs. 78.6% p = 0.048). Mean overall survival duration from symptom onset was significantly longer in female than male patients (female: 39.2 ± 29.04 months; male: 29.4 ± 24.06 months, P = 0.03). In the multivariable Cox regression model, bulbar onset (aHR = 5.28, p = 0.035) correlated with poor survival outcome while longer duration from onset to second symptom (aHR = 0.96, P = 0.037) indicated better survival. CONCLUSIONS: Bulbar onset was a significant risk predictor for survival. Slower disease progression correlated with better outcomes. Age of onset may differ among ethnic groups. Male patients are more likely to develop Amyotrophic Lateral Sclerosis (ALS) and have shorter survival duration.

Intraoperative Motor Evoked Potential Improvement in Cervical Spondylotic Myelopathy: Comparison of Cortical Stimulation Parameters.

BACKGROUND AND PURPOSE: Intraoperative monitoring of the motor pathways is a routine procedure for ensuring the integrity of descending motor tracts during spinal surgery. Intraoperative motor evoked potential improvement (MEPI) may be associated with a better postsurgical outcome in cervical spondylotic myelopathy (CSM). To compare the efficacy of two cortical stimulation parameters in eliciting MEPI intraoperatively during CSM surgery. METHODS: We studied 69 patients who underwent decompression surgery for CSM over a 9-month period using either 5 (Group 1) or 9 (Group 2) stimuli. MEPI was defined as the increase in the amplitude of MEPs from baseline at the end of CSM surgery just prior to skin closure. RESULTS: An MEPI of 100% from baseline was observed in 10 patients (53%) in Group 1 and 36 patients (72%) in Group 2. Comparisons of the baseline mean MEP amplitudes of muscles bilaterally between Groups 1 and 2 did not reveal any significant differences. Supramaximal stimulation showed that a significantly higher mean intensity was required for Group 1 than for Group 2. CONCLUSIONS: MEPI is observed in a much larger proportion of cervical decompression surgery cases than previously thought. Intraoperative MEPI with longer-train cortical stimulation may reflect adequacy of decompression and provide additional guidance for the surgical procedure.

Impact of Cryotherapy on Sensory, Motor, and Autonomic Neuropathy in Breast Cancer Patients Receiving Paclitaxel: A Randomized, Controlled Trial.

Introduction: We conducted a randomized controlled trial evaluating the efficacy and tolerability of cryotherapy in preventing chemotherapy-induced peripheral neuropathy (CIPN) in patients with early breast cancer receiving neo/adjuvant weekly paclitaxel. Methods: Patients were recruited from the National Cancer Centre Singapore and randomized (1:1) to receive either cryotherapy or usual care. Cryotherapy was applied as frozen gloves and socks on all extremities from 15 min before paclitaxel until 15 min post-infusion every cycle. Efficacy was measured by patient-reported outcomes (Patient Neurotoxicity Questionnaire [PNQ] and EORTC QLQ-CIPN20) and electrophysiological assessments. The primary endpoint was PNQ severity at 2 weeks after 12 cycles of weekly paclitaxel. Results: A total of 46 patients were recruited, of which 8 dropped out before paclitaxel treatment, leaving 38 evaluable. There was no significant difference in PNQ severity between cryotherapy and usual care at 2 weeks after paclitaxel treatment (sensory: p = 0.721; motor: p = 1.000). A benefit was observed at 3 months post-paclitaxel based on PNQ (sensory: 14.3 vs. 41.2%, p = 0.078; motor: 0 vs. 29.4%, p = 0.012) and CIPN20 (sensory: ß = -3.6, 95%CI = -10.5-3.4, p = 0.308; motor: ß = -7.3, 95%CI = -14.6-0, p = 0.051). Additionally, cryotherapy subjects have lower CIPN20 autonomic score (ß = -5.84, 95%CI = -11.15 to -0.524, p = 0.031) and higher sympathetic skin response hand amplitudes (ß = 0.544, 95%CI = 0.108-0.98, p = 0.014), suggesting possible autonomic benefits from cryotherapy. Temporary interruption with cryotherapy occurred in 80.9% of the subjects due to cold intolerance. Conclusions: There is insufficient evidence that cryotherapy prevents sensory neuropathy which may be due to the high rates of cryotherapy interruption in this study. The autonomic benefits of cryotherapy should be further investigated with appropriate outcome measures. Clinical Trial Registration: ClinicalTrials.gov: NCT03429972.

Immunotherapy for diabetic amyotrophy.

BACKGROUND: People with diabetes mellitus (DM) sometimes present with acute or subacute, progressive, asymmetrical pain and weakness of the proximal lower limb muscles. The various names for the condition include diabetic amyotrophy, or diabetic lumbosacral radiculoplexus neuropathies. Some studies suggest that it may be due to immune-mediated inflammatory microvasculitis causing ischaemic damage of the nerves. Immunotherapies would therefore be expected to be beneficial. OBJECTIVES: We aimed to review the evidence from randomised trials for the efficacy of any form of immunotherapy in the treatment of diabetic amyotrophy. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials Register (searched April 2 2009), MEDLINE (searched January 1966 to April 2 2009), EMBASE (searched January 1980 to April 2 2009) and contacted authors of relevant publications and other experts to obtain additional references, unpublished trials, and ongoing trials. SELECTION CRITERIA: We intended to include all randomised and quasi-randomised trials of any immunotherapy in participants with the condition fulfilling all the following: diabetes mellitus as defined by internationally recognised criteria, acute or subacute onset of pain and lower motor neuron weakness involving predominantly the proximal muscles of the lower limbs, weakness that is not confined to one nerve or nerve root distribution and exclusion of other causes of lumbosacral radiculopathies and plexopathy. DATA COLLECTION AND ANALYSIS: Two authors independently examined all references retrieved by the search to select those meeting the inclusion criteria. MAIN RESULTS: We found only one completed controlled trial using intravenous methylprednisolone in diabetic amyotrophy (Dyck 2006). The results have not been fully published and were not available for analyses. AUTHORS' CONCLUSIONS: There is presently no evidence from randomised trials to support any recommendation on the use of any immunotherapy treatment in diabetic amyotrophy.

Stiff Person Syndrome Associated with Compartment Syndrome.

Stiff person syndrome (SPS) is a rare and disabling neurological disorder of autoimmune origin, characterized by progressive stiffness and muscle spasms affecting the axial and limb muscles, most frequently associated with antibodies against glutamic acid decarboxylase. We describe a patient who presented initially with compartment syndrome and was later diagnosed with SPS. This is the first case report of SPS possibly presenting initially with compartment syndrome. This case illustrates the importance of recognizing that patients with SPS may present with varied manifestations, including compartment syndrome, which by itself is a medical emergency.