Neil G. Simon

Expanding the clinical, radiological and neuropathological phenotype of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS)

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently described inflammatory disease of the CNS with a predilection for the hindbrain and responsive to immunotherapy. Five further cases are described with detailed pathology and long term evaluation. CLIPPERS does not represent a benign condition, and without chronic immunosuppression the disease may relapse. The radiological distribution is focused not only in the pons but also in the brachium ponti and cerebellum. Pontocerebellar atrophy occurred early, even in cases treated promptly. Significant cognitive impairment was seen in some cases and was associated with additional cerebral atrophy. The pathology included distinctive histiocytic as well as lymphocytic components and evidence of neuro-axonal injury. Additional subclinical systemic findings on investigation were identified. Relapse was associated with withdrawal of corticosteroids, and disability was least marked in cases where both the presentation and relapses were treated promptly. We propose that the title of the syndrome be amended to chronic lymphocytic inflammation with pontocerebellar perivascular enhancement responsive to steroids to more accurately reflect the distribution of the radiological findings.

Quantifying Disease Progression in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) exhibits characteristic variability of onset and rate of disease progression, with inherent clinical heterogeneity making disease quantitation difficult. Recent advances in understanding pathogenic mechanisms linked to the development of ALS impose an increasing need to develop strategies to predict and more objectively measure disease progression. This review explores phenotypic and genetic determinants of disease progression in ALS, and examines established and evolving biomarkers that may contribute to robust measurement in longitudinal clinical studies. With targeted neuroprotective strategies on the horizon, developing efficiencies in clinical trial design may facilitate timely entry of novel treatments into the clinic. Ann Neurol 2014;76:643–657

Ultrasound in the diagnosis of peripheral neuropathy: structure meets function in the neuromuscular clinic

Peripheral nerve ultrasound (US) has emerged as a promising technique for the diagnosis of peripheral nerve disorders. While most experience with US has been reported in the context of nerve entrapment syndromes, the role of US in the diagnosis of peripheral neuropathy (PN) has recently been explored. Distinctive US findings have been reported in patients with hereditary, immune-mediated, infectious and axonal PN; US may add complementary information to neurophysiological studies in the diagnostic work-up of PN. This review describes the characteristic US findings in PN reported to date and a classification of abnormal nerve US patterns in PN is proposed. Closer scrutiny of nerve abnormalities beyond assessment of nerve calibre may allow for more accurate diagnostic classification of PN, as well as contribute to the understanding of the intersection of structure and function in PN.

A novel tool to detect behavioural symptoms in ALS

Abstract There is need for a valid, sensitive and short instrument capable of detecting and quantifying behavioural changes in ALS, which can be utilized in clinical and research settings. This study aimed to 1) develop and validate such an instrument; 2) verify the most common behavioural symptoms; and 3) investigate longitudinal changes over a six-month period. Two hundred and nineteen patients were included. The development sample (n = 140) was used to determine the most appropriate items to include in the new tool, the Motor Neuron Disease Behavioural Instrument (MiND-B), via a data-driven approach. An independent sample (n = 79) validated the tool. A more comprehensive sample (n = 50, sub-classified into ALS and ALS plus) was utilized to verify if the MiND-B could detect ALS plus patients. Finally, 20 ALS patients completed the MiND-B after a six-month period. Apathy, disinhibition and stereotypical behaviour were all found to be very common symptoms in ALS occurring in 75%, 66% and 58%, respectively, of cases. Notably, the MiND-B could identify ALS plus patients without standard cognitive assessments. In conclusion, the MiND-B tool can detect patients with ALS plus reliably, by means of questions to the informant. This test could enable ALS centres to evaluate non-motor symptoms and adapt management and decision-making approaches as necessary. *only available in the online version of the journal. Please find this material with the following direct link to the article: http://www.informahealthcare.com/(DOI: 10.3109/21678421.2014.896927)

High-resolution ultrasonography and diffusion tensor tractography map normal nerve fascicles in relation to schwannoma tissue prior to resection

The goals of the present study were to demonstrate the ability of high-resolution ultrasonography to delineate normal nerve fascicles within or around peripheral nerve sheath tumors (NSTs). A blinded examiner evaluated 2 patients with symptomatic upper limb NSTs with high-resolution ultrasonography performed in the perioperative suite using a portable ultrasonography system. Ultrasonographic examinations located the tumor mass and identified the normal nerve fascicles associated with the mass. The locations of normal nerve tissue were mapped and correlated with results of MR tractography, operative inspection, and intraoperative electrophysiological monitoring. The study demonstrated a close correlation between normal nerve fascicles identified by ultrasonography, MR tractography, and intraoperative electrophysiological mapping. In particular, ultrasonographic examinations accurately identified the surface regions of the tumor without overlying normal nerve tissue. These preliminary data suggest that preoperative ultrasonographic examinations may provide valuable information, supplementary to the information obtained from intraoperative electrophysiological monitoring. Identification of normal nerve tissue prior to surgery may provide additional information regarding the risk of iatrogenic nerve injury during percutaneous tumor biopsy or open resection of the tumor and may also aid in selecting the optimum surgical approach.

Assessment of the upper motor neuron in amyotrophic lateral sclerosis

Clinical signs of upper motor neuron (UMN) involvement are an important component in supporting the diagnosis of amyotrophic lateral sclerosis (ALS), but are often not easily appreciated in a limb that is concurrently affected by muscle wasting and lower motor neuron degeneration, particularly in the early symptomatic stages of ALS. Whilst recent criteria have been proposed to facilitate improved detection of lower motor neuron impairment through electrophysiological features that have improved diagnostic sensitivity, assessment of upper motor neuron involvement remains essentially clinical. As a result, there is often a significant diagnostic delay that in turn may impact institution of disease-modifying therapy and access to other optimal patient management. Biomarkers of pathological UMN involvement are also required to ensure patients with suspected ALS have timely access to appropriate therapeutic trials. The present review provides an analysis of current and recently developed assessment techniques, including novel imaging and electrophysiological approaches used to study corticomotoneuronal pathology in ALS.

Advances in the neurological and neurosurgical management of peripheral nerve trauma

Peripheral nerve trauma frequently affects younger people and may result in significant and long-lasting functional disability. Currently, diagnosis and monitoring of peripheral nerve injury relies on clinical and electrodiagnostic information, supplemented by intraoperative electrophysiological studies. However, in a significant proportion of nerve injuries, the likelihood of spontaneous regeneration resulting in good functional outcome remains uncertain and unnecessary delays to treatment may be faced while monitoring for recovery. Advances in non-invasive imaging techniques to diagnose and monitor nerve injury and regeneration are being developed, and have the potential to streamline the decision-making process. In addition, advances in operative and non-operative treatment strategies may provide more effective ways to maximise functional outcomes following severe peripheral nerve trauma. This review discusses these advances in light of the current state of the art of management of peripheral nerve trauma.

Patterns of clinical and electrodiagnostic abnormalities in early amyotrophic lateral sclerosis.

Introduction: The distribution of clinical and neurophysiological abnormalities in patients with early amyotrophic lateral sclerosis (ALS) was investigated in an attempt to delineate patterns of disease spread. Methods: Clinical and electrodiagnostic data were collected from 150 ALS patients and analyzed based on the clinical region of onset. Results: Asymmetry of clinical and neurophysiological abnormalities was more marked in upper limb‐onset than lower limb‐onset disease. Significant rostral–caudal gradients of clinical weakness were identified in bulbar‐ and lower limb‐onset disease. Neurophysiological evidence of the ALS “split‐hand” pattern was evident irrespective of the region of disease onset. Limbs with and without evidence of clinical weakness demonstrated similar rates of abnormality on electromyography. Conclusions: These findings suggest a pattern of disease spread in ALS. This study may serve to guide ongoing development of disease quantitation biomarkers and the targeting of future neuroprotective strategies. Muscle Nerve 50: 894–899, 2014

Peripheral nerve diffusion tensor imaging is reliable and reproducible.

To determine the reliability and reproducibility of peripheral nerve diffusion tensor imaging (DTI) in healthy subjects.

Visualizing axon regeneration after peripheral nerve injury with magnetic resonance tractography

Diffusion tensor imaging (DTI) with tractography is an MRI technique that can visualize nerve pathways by taking advantage of anisotropy of water diffusion in tracts with longitudinally oriented fibers. To date, no study in humans has shown that DTI and tractography can follow regeneration of axons during recovery from traumatic peripheral nerve injury. We show that tractography is able to identify regenerating axons advancing through a graft repair of an injured nerve, and demonstrate correlation with evidence of recovery on serial clinical, electrodiagnostic, and muscle MRI assessments.