Utility of Paraneoplastic Antibody Testing in the Diagnosis of Motor Neuron Disease.

OBJECTIVE: To evaluate the role of paraneoplastic autoantibody testing in the diagnosis of motor neuron disease (MND). BACKGROUND: There have been rare case reports of paraneoplastic MND that have prompted many physicians to test for paraneoplastic autoantibodies in patients with MND. Our study is the first to determine the utility of such testing. METHODS: Retrospective chart review of patients with MND from a tertiary referral center from 2007 to 2014. RESULTS: Of 316 patients with MND reviewed, 44% (n = 138) were evaluated by a Mayo Clinic paraneoplastic autoantibody panel. Of note, 73% of these patients (n = 101) were diagnosed with amyotrophic lateral sclerosis, fulfilling possible, probable, or definite revised El Escorial criteria. Of note, 9% of patients (13/138) of those who had paraneoplastic antibody testing performed were positive for at least 1 paraneoplastic antibody. Three patients had negative testing for malignancy. None had a different disease course than expected. CONCLUSIONS: Testing for paraneoplastic antibodies does not seem to change the diagnosis, management, or outcome in the setting of MND and is therefore of limited value.

Prospective evaluation of a new classification system for the management of mandibular subcondylar fractures.

PURPOSE: We propose a new classification of subcondylar fractures of the mandible based on ramal height shortening and degree of fracture angulation and present our treatment experience using this classification system. PATIENTS AND METHODS: Eighty patients with subcondylar fractures of the mandible were evaluated. We categorized the fractures into 3 classes: Class 1 (minimally displaced), fracture with ramal height shortening: <2 mm and/or degree of fracture displacement: <10°; Class 2 (moderately displaced), fracture with ramal height shortening: 2 to 15 mm and/or degree of fracture displacement: 10 to 35°; Class 3 (severely displaced), fracture with ramal height shortening: >15 mm and/or degree of fracture displacement: >35°. Our treatment protocol is closed treatment for Class 1 fractures; either closed or open treatment for Class 2 fractures; and open treatment for Class 3 fractures. RESULTS: Among 80 patients, 20 had Class 1 fractures (25%), 40 had Class 2 fractures (50%), and 20 had Class 3 fractures (25%). In Class 2 fractures, 22 patients were managed by closed treatment (Class 2a) and 18 by open treatment (Class 2b). No statistically significant differences were found between the 3 classes in terms of functional outcome, while, within Class 2 patients, significantly (P = .00) better functional results were observed in open (Class 2b) group compared with closed group (Class 2a). CONCLUSIONS: Our new classification based on ramal height shortening and degree of fracture displacement can better guide clinical treatment. Class 1 fractures are treated by closed method, while open reduction is recommended in Class 2 and Class 3 cases.

Motor neurone disease: a practical update on diagnosis and management.

Motor neurone disease (MND) is an adult-onset neurodegenerative disease which leads inexorably via weakness of limb, bulbar and respiratory muscles to death from respiratory failure three to five years later. Most MND is sporadic but approximately 10% is inherited. In exciting recent breakthroughs two new MND genes have been identified. Diagnosis is clinical and sometimes difficult--treatable mimics must be excluded before the diagnosis is ascribed. Riluzole prolongs life by only three to four months and is only available for the amyotrophic lateral sclerosis (ALS) form of MND. Management therefore properly focuses on symptom relief and the preservation of independence and quality of life. Malnutrition is a poor prognostic factor. In appropriate patients enteral feeding is recommended although its use has yet to be shown to improve survival. In ALS patients with respiratory failure and good or only moderately impaired bulbar function non-invasive positive pressure ventilation prolongs life and improves quality of life.

Muscle histopathology in upper motor neuron-dominant amyotrophic lateral sclerosis.

The distinction between primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS) still remains debated. Recently, PLS patients displaying lower motor neuron (LMN) signs have been defined as 'upper motor neuron (UMN)-dominant ALS', using 'clinically pure PLS' diagnosis to those with no LMN signs. To further characterize the LMN involvement in UMN-dominant ALS we investigated the presence and the extent of neurogenic abnormalities in the skeletal muscle of patients affected with a pyramidal syndrome consistent with UMN-dominant ALS. A total of nine patients affected with UMN-dominant ALS were analysed. In all cases, muscle biopsies showed the presence of scattered or clustered atrophic angulated fibres in small groups, and a mild to moderate fibre type-grouping. Target and targetoid fibres were detected in two cases only. Three patients had a second muscle biopsy which demonstrated a roughly unchanged pattern of chronic denervation with still moderate reinnervation phenomena. This study suggests that in UMN-dominant ALS muscle denervation may be characterized by an early chronic impairment of a restricted number of LMNs. The extent rather than the presence of LMN signs may allow to categorize patients with motor neuron disease involving mainly UMN into distinct entities.

Are enteroviral receptors different in sporadic motor neuron disease?

Enteroviruses have been suspected to play a part in the pathogenesis of sporadic motor neuron disease (SMND). Intercellular adhesion molecule type-1 (ICAM1) and coxsackie and adenovirus receptor (CAR) act as receptors for a number of enteroviruses. We therefore examined the viral binding domains of ICAM1 and CAR to see if any changes could be found that might predispose to enteroviral infections. Single nucleotide polymorphisms in the ICAM1 viral binding domain, the adjacent intron and a region implicated in other neurological disorders, as well as the CAR viral binding regions in exons 2-5, were compared in 139 SMND patients and 139 matched controls. The distribution of the polymorphisms was similar in both groups. Therefore, based on linkage disequilibrium and genotype it is unlikely that either ICAM1 or CAR is implicated in SMND.

Chronic dysimmune neuropathy. A subclassification based upon the clinical features of 102 patients.

The Chronic Dysimmune neuropathies (CDN) are a clinically heterogeneous group of polyneuropathies united by their presumed immune mediated aetiology. At present such neuropathies are classified as Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), Multifocal Motor Neuropathy (MMN) and the Neuropathies in association with serum Paraproteins (Paraproteinaemic Neuropathies). This classification fails to recognise other distinctive syndromes and is limited by heterogeneity within, and overlap between, subgroups. We have refined this clinical subclassification by a review of a consecutive series of 102 unselected patients with CDN referred to a single neurologist. We recognise 6 clinical subtypes of CDN: one sensory ataxic group; three motor-sensory subgroups (chronic motor sensory demyelinating neuropathy, subacute motor sensory demyelinating neuropathy and a multifocal motor sensory neuropathy); and two pure motor subgroups (symmetric pure motor demyelinating neuropathy and multifocal motor neuropathy). This subclassification allows distinct syndromes to be recognised and helps resolve problems of heterogeneity and overlap. Distinction between these subgroups is of immediate practical relevance to patient management. Although steroids are beneficial for most of the subgroups, this is not so for both of the pure motor syndromes which should be treated with intravenous immunoglobulin. Patients with chronic development of Motor Sensory Demyelinating Neuropathy respond less well to steroids than those with a subacute onset. An association was found between elderly patients with Subacute Motor Sensory Demyelinating Neuropathy and carcinomas. Within any clinical subgroup patients behave similarly regardless of the presence of associated paraproteins or nerve specific antibodies.

Motor neuron disease: classification and nomenclature.

The classification and nomenclature of motor neuron disease, whether sporadic or familial, is confused. For example, both the sporadic and familial motor neuron diseases are phenotypically heterogeneous and, in familial ALS, phenotypic heterogeneity correlates only weakly with different underlying mutations in the SOD1 gene. We propose a classification which is based on underlying causative mechanisms, where these are known, but which also recognizes different clinical phenotypes when the cause is unknown. This classification is flexible, and allows reattribution of clinical syndromes when their causation is understood. Currently uncertain associations--for example, a possible association of ALS with cancer--are given tentative recognition in this classification. In addition, this new classification recognizes geographical clustering and descriptions of unusual motor neuron disorder phenotypes of unknown origin in different parts of the world.

Multifocal acquired demyelinating sensory and motor neuropathy: the Lewis-Sumner syndrome.

We report 11 patients with multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy, defined clinically by a multifocal pattern of motor and sensory loss, with nerve conduction studies showing conduction block and other features of demyelination. The clinical, laboratory, and histological features of these patients were contrasted with those of 16 patients with multifocal motor neuropathy (MMN). Eighty-two percent of MADSAM neuropathy patients had elevated protein concentrations in the cerebrospinal fluid, compared with 9% of the MMN patients (P < 0.001). No MADSAM neuropathy patient had elevated anti-GM1 antibody titers, compared with 56% of MMN patients (P < 0.01). In contrast to the subtle abnormalities described for MMN, MADSAM neuropathy patients had prominent demyelination on sensory nerve biopsies. Response to intravenous immunoglobulin treatment was similar in both groups (P = 1.0). Multifocal motor neuropathy patients typically do not respond to prednisone, but 3 of 6 MADSAM neuropathy patients improved with prednisone. MADSAM neuropathy more closely resembles chronic inflammatory demyelinating polyneuropathy and probably represents an asymmetrical variant. Given their different clinical patterns and responses to treatment, it is important to distinguish between MADSAM neuropathy and MMN.