Assessment of diagnostic criteria for multifocal motor neuropathy in patients included in the Italian database.

BACKGROUND AND PURPOSE: This study aimed to assess the diagnostic criteria, ancillary investigations and treatment response using real-life data in multifocal motor neuropathy (MMN) patients. METHODS: Clinical and laboratory data were collected from 110 patients enrolled in the Italian MMN database through a structured questionnaire. Twenty-six patients were excluded due to the unavailability of nerve conduction studies or the presence of clinical signs and symptoms and electrodiagnostic abnormalities inconsistent with the MMN diagnosis. Analyses were conducted on 73 patients with a confirmed MMN diagnosis and 11 patients who did not meet the diagnostic criteria. RESULTS: The European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) diagnostic criteria were variably applied. AUTHOR: When applying the American Association of Electrodiagnostic Medicine criteria, an additional 17% of patients fulfilled the criteria for probable/definite diagnosis whilst a further 9.5% missed the diagnosis. In 17% of the patients only compound muscle action potential amplitude, but not area, was measured and subsequently recorded in the database by the treating physician. Additional investigations, including anti-GM1 immunoglobulin M antibodies, cerebrospinal fluid analysis, nerve ultrasound and magnetic resonance imaging, supported the diagnosis in 46%-83% of the patients. Anti-GM1 immunoglobulin M antibodies and nerve ultrasound demonstrated the highest sensitivity. Additional tests were frequently performed outside the EFNS/PNS guideline recommendations. CONCLUSIONS: This study provides insights into the real-world diagnostic and management strategies for MMN, highlighting the challenges in applying diagnostic criteria.

Electrodiagnostic Assessment of Motor Neuron Disease.

Motor neuron diseases involve degeneration of motor neurons in the brain (upper motor neurons), brain stem, and spinal cord (lower motor neurons). Symptoms vary depending on the degree of upper and lower neuron involvement, but progressive painless weakness is the predominant complaint. Motor neuron disease includes numerous specific disorders, including amyotrophic lateral sclerosis, spinal muscular atrophy, spinal bulbar muscular atrophy, and other inherited and acquired conditions. Abnormalities on nerve conduction studies, repetitive nerve stimulation, needle electromyography, and other electrodiagnostic techniques help to distinguish these disorders from each other, and from other disorders with progressive weakness.

Validity and reliability of an electromyography-based upper limb assessment quantifying selective voluntary motor control in children with upper motor neuron lesions.

Current clinical assessments evaluating selective voluntary motor control are measured on an ordinal scale. We combined the Selective Control of the Upper Extremity Scale (SCUES) with surface electromyography to develop a more objective and interval-scaled assessment of selective voluntary motor control. The resulting Similarity Index (SI) quantifies the similarity of muscle activation patterns. We aimed to evaluate the validity and reliability of this new assessment named SISCUES (Similarity Index of the SCUES) in children with upper motor neuron lesions. Thirty-three patients (12.2 years [8.8;14.9]) affected by upper motor neuron lesions with mild to moderate impairments and 31 typically developing children (11.6 years [8.5;13.9]) participated. We calculated reference muscle activation patterns for the SISCUES using data of 33 neurologically healthy adults (median [1st; 3rd quantile]: 32.5 [27.9; 38.3]). We calculated Spearman correlations (ρ) between the SISCUES and the SCUES and the Manual Ability Classification System (MACS) to establish concurrent validity. Discriminative validity was tested by comparing scores of patients and healthy peers with a robust ANCOVA. Intraclass correlation coefficients2,1 and minimal detectable changes indicated relative and absolute reliability. The SISCUES correlates strongly with SCUES (ρ = 0.76, p < 0.001) and moderately with the MACS (ρ = -0.58, p < 0.001). The average SISCUES can discriminate between patients and peers. The intraclass correlation coefficient2,1 was 0.90 and the minimal detectable change was 0.07 (8% of patients' median score). Concurrent validity, discriminative validity, and reliability of the SISCUES were established. Further studies are needed to evaluate whether it is responsive enough to detect changes from therapeutic interventions.

National audit of cognitive assessment in people with pwMND A national audit of cognitive assessment in people with motor neurone disease (pwMND) in Scotland.

Cognitive and behavioral abnormalities are recognized as an integral part of Motor Neurone Disease (MND) and occur at all stages of the disease. The early detection of cognitive and behavioral symptoms in MND is critical. Such symptoms are only reported when we explicitly ask, evaluate, document, and assess. In the National Institute for Health and Care Excellence (NICE) MND guideline (2016), formal cognitive and behavioral assessment is incorporated in MND management and is fundamental to providing appropriate care to pwMND. Cognition is explicitly stated in 14 separate recommendations in the guidelines. The NICE guidelines therefore constitute pre-defined standards which we audited. This audit highlights that health professionals increasingly recognize the significance of cognitive screening in MND and follow more structured approaches in implementing this compared to previous years.

Longitudinal multi-modal muscle-based biomarker assessment in motor neuron disease.

BACKGROUND: Clinical phenotypic heterogeneity represents a major barrier to trials in motor neuron disease (MND) and objective surrogate outcome measures are required, especially for slowly progressive patients. We assessed responsiveness of clinical, electrophysiological and radiological muscle-based assessments to detect MND-related progression. MATERIALS AND METHODS: A prospective, longitudinal cohort study of 29 MND patients and 22 healthy controls was performed. Clinical measures, electrophysiological motor unit number index/size (MUNIX/MUSIX) and relative T2- and diffusion-weighted whole-body muscle magnetic resonance (MR) were assessed three times over 12 months. Multi-variable regression models assessed between-group differences, clinico-electrophysiological associations, and longitudinal changes. Standardized response means (SRMs) assessed sensitivity to change over 12 months. RESULTS: MND patients exhibited 18% higher whole-body mean muscle relative T2-signal than controls (95% CI 7-29%, p < 0.01), maximal in leg muscles (left tibialis anterior 71% (95% CI 33-122%, p < 0.01). Clinical and electrophysiological associations were evident. By 12 months, 16 patients had died or could not continue. In the remainder, relative T2-signal increased over 12 months by 14-29% in right tibialis anterior, right quadriceps, bilateral hamstrings and gastrocnemius/soleus (p < 0.01), independent of onset-site, and paralleled progressive weakness and electrophysiological loss of motor units. Highest clinical, electrophysiological and radiological SRMs were found for revised ALS-functional rating scale scores (1.22), tibialis anterior MUNIX (1.59), and relative T2-weighted leg muscle MR (right hamstrings: 0.98), respectively. Diffusion MR detected minimal changes. CONCLUSION: MUNIX and relative T2-weighted MR represent objective surrogate markers of progressive denervation in MND. Radiological changes were maximal in leg muscles, irrespective of clinical onset-site.

Exploring patient and public involvement in motor neuron disease research.

Objectives: Patient and public involvement (PPI) is a relatively new practice whereby researchers involve patients and the public in the conduct of their research. The Sheffield Motor Neurone Disorders Research Advisory Group (SMNDRAG) is one of the first groups to specialise in motor neuron disease (MND). Its members include people living with MND, carers, relatives, volunteers, clinicians, and scientists. Our aim was to explore the experiences of those who participate in, organise and work with the SMNDRAG. Methods: We conducted 13 semi-structured interviews: 10 with members of the SMNDRAG and three with researchers who have worked with the group. We used thematic analysis to identify ways in which the group influenced research and the barriers and enablers to PPI. Results: A number of motivations for participating in the SMNDRAG were reported but the majority were altruistic. The SMNDRAG offered individuals psychosocial and intellectual benefits. The SMNDRAG has overcome a number of practical and psychological barriers to developing a successful and effective collaborative partnership resulting in a positive impact on research and researchers at each stage of the research process. For example, the group identified research priorities which ensured that research was patient-focused. However, several barriers remain, including the lack of diversity within the group and the perception that PPI participation requires a "certain type of person." Conclusions: PPI can make a valuable contribution to all aspects of research and can have a positive impact on those involved. We recommend ways in which PPI can and should be incorporated into research.

Electrophysiological Assessment and Classification of Motor Pathway Function in Patients With Spinal Dural Arteriovenous Fistula.

PURPOSE: The diagnosis of spinal dural arteriovenous fistula (SDAVF) is difficult and often delayed because clinical features are often nonspecific. We assessed the motor function electrophysiologically in patients with SDAVF. METHODS: Motor-evoked potentials after transcranial magnetic stimulation and compound muscle action potentials and F-waves after electrical stimulation in the ulnar and tibial nerves were measured from the abductor hallucis (AH) muscles in 14 patients with SDAVF (SDAVF group), 12 patients with compressive thoracic myelopathy (CTM group), and 16 normal subjects (control group). The peripheral conduction time determined from abductor hallucis muscles (PCT-AH) and the central motor conduction time determined from abductor hallucis muscles (CMCT-AH) were calculated. According to the neurological findings, patients in the SDAVF group were classified to upper motor neuron (UMN) sign and lower motor neuron (LMN) sign categories. RESULTS: CMCT-AH in the SDAVF and CMT groups were significantly longer than those in the control group. PCT-AH in the SDAVF group was significantly longer than that in the control and CMT groups. Twelve patients in the SDAVF group showed abnormal CMCT-AH and/or PCT-AH. Abnormal CMCT-AH and PCT-AH were detected in five cases that exhibited UMN sign and/or LMN sign. Three cases with abnormal CMCT-AH and normal PCT-AH exhibited UMN sign. LMN sign without UMN sign was observed in four cases with abnormal PCT-AH and normal CMCT-AH. CONCLUSIONS: Our study revealed abnormalities in the corticospinal tract and/or lower motor neurons, and classified the patients with SDAVF into three types: the UMN type, LMN type, and mixed type.

Meaningful Assessment in Patients with Acquired Brain Injuries.

There are several key components to the meaningful and comprehensive assessment of patients with acquired brain injuries with respect to management of the upper motor neuron syndrome. Type of brain injury, trajectory of recovery, relevant concomitant complications, development of appropriate goals, and an understanding of resources available for patients are all factors to assess when developing a treatment plan. Using appropriate outcome measures will help monitor the efficacy of interventions and guide ongoing management of spasticity.

Motoneuron diseases: impact on health professionals.

The approach to patients affected by motor neuron disease (MND) and their caregivers requires specific training for the care-team. In fact, the progression of the disease, with the decline of physical--and sometimes cognitive--function, the increasing difficulties in speaking, breathing, and swallowing and the need of invasive choices, as the artificial nutrition and tracheostomy, constitute a challenge for the health professionals, often generating distress. For this reason, their cohesion and sharing abilities are fundamental. Psychologist assumes a strategic role in supporting and facilitating the analysis of clinical cases and of the team's intra/interpersonal dynamics. For this aim, he/she needs specific training and instruments. We here present a semi-structured interview--the Motor Neuron Disease-Psychological Interview (MoNeDi-PI)--which may guide in the psychological assessment of patients affected by MNDs and their caregivers. It can also be a handy reference tool for other members of the healthcare team providing necessary information about the patient and caregiver in order to optimize clinical decision making about which health interventions to apply.

Diagnostic yield and cost-effectiveness of investigations in patients presenting with isolated lower motor neuron signs.

Our objective was to investigate the yield and cost-effectiveness of investigations and therapeutic trials of intravenous immunoglobulin (IVIg) in patients presenting with isolated lower motor neuron (LMN) signs. We performed a retrospective chart review of cases diagnosed between January 2007 and September 2013. Investigation results and their impact on outcome, and outcome of IVIg treatment trials were abstracted. Cost was calculated in Canadian dollars (C$). Fifty-nine of 333 patients presented with isolated LMN signs. The majority of patients (61%) evolved to amyotrophic lateral sclerosis (ALS) within 36 months of presentation, while 37.3% remained with progressive muscular atrophy (PMA) with mean follow-up 29.6 months. Of the 1210 tests performed, 4.9% were abnormal. The diagnosis was changed in only one patient where a muscle biopsy revealed a distal myopathy. Fourteen patients received therapeutic trials of IVIg to rule out an IVIg-responsive inflammatory motor neuropathy with no objective clinical benefit. Total group cost was C$630,484.72 (C$10,686.18/patient). IVIg represented 58.7% of total costs. In conclusion, extensive investigations and treatment trials of IVIg have low yield in the work-up of patients with isolated LMN signs and are not cost-effective when clinical features do not suggest an alternative diagnosis to PMA.

Correlates of muscle strength in diabetes: The study on the assessment of determinants of muscle and bone strength abnormalities in diabetes (SAMBA).

BACKGROUND AND AIMS: Apart from late motor nerve dysfunction, factors affecting muscle strength in diabetes are largely unknown. This study was aimed at assessing muscle strength correlates in diabetic subjects encompassing a wide range of peripheral nerve function and various degrees of micro and macrovascular complications. METHODS AND RESULTS: Four-hundred consecutive patients with type 1 and 2 diabetes (aged 46.4 ± 13.9 and 65.8 ± 10.3 years, respectively) from the Study on the Assessment of Determinants of Muscle and Bone Strength Abnormalities in Diabetes (SAMBA) were examined for upper and lower body muscle isometric maximal voluntary contraction by dynamometry. Univariate and multivariate regression analyses were applied to identify strength correlates. Isometric force at both the upper and lower limbs was significantly lower in subjects with than in those without any complication. At univariate analysis, it was strongly associated with age, diabetes duration, physical activity (PA) level, cardio-respiratory fitness, anthropometric parameters, surrogate measures of complications, and parameters of sensory and autonomic, but not motor (except amplitude) neuropathy. Multivariate analysis revealed that upper and lower body strength correlated independently with male gender and, inversely, with age, autonomic neuropathy score (or individual autonomic function abnormalities), and vibration perception threshold, but not sensory-motor neuropathy score. Diabetes duration and PA level were excluded from the model. CONCLUSIONS: Both upper and lower body muscle strength correlate with measures of diabetic complications and particularly with parameters of sensory and especially autonomic nerve function, independently of diabetes duration and PA level, thus suggesting the involvement of mechanisms other than manifest motor nerve impairment.

Congenital hypotonia: clinical and developmental assessment.

Identifying the underlying cause of congenital hypotonia remains difficult, despite advances in diagnostic laboratory and imaging techniques. Clinical evaluation strategies and standardized developmental tests can assist in differentiating hypotonia resulting from primary involvement of the upper motoneuron (central hypotonia) versus that involving the lower motoneuron and motor unit (peripheral hypotonia). This is especially important in infants with idiopathic hypotonia. This review outlines and describes the components of the clinical assessment: detailed infant and family history, clinical techniques and characteristics for differentiating hypotonia of central versus peripheral origin, and clinical evaluation (muscle tone, primitive reflexes, deep tendon reflexes, etc). Recent research that has contributed to the differential diagnosis of congenital hypotonia is reviewed and directions for future research are provided. Ideally, the assessment of infants with congenital hypotonia is best accomplished by an interdisciplinary team of developmental specialists including pediatricians, medical geneticists, child neurologists, and physical or occupational therapists.

American Association of Neuromuscular & Electrodiagnostic Medicine evidenced-based review: use of surface electromyography in the diagnosis and study of neuromuscular disorders.

Surface electromyography (sEMG) measures myoelectrical signals recorded from sensors placed on the skin surface. The non-invasive nature of sEMG makes it a potentially useful technology for studying diseases of muscle and nerve. Reviews published by the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) and the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (AAN), covering 1964-1994 and 1952-1998, respectively, concluded that sEMG adds no clinical utility over conventional needle EMG (nEMG) for the diagnosis of neuromuscular disease. The AANEM sEMG task force reevaluated the diagnostic utility and added value of this technology for the study of neuromuscular disease based on a contemporary review of relevant literature published between January 1994 and February 2006. The present review concludes that sEMG may be useful to detect the presence of neuromuscular disease (level C rating, class III data), but there are insufficient data to support its utility for distinguishing between neuropathic and myopathic conditions or for the diagnosis of specific neuromuscular diseases. sEMG may be useful for additional study of fatigue associated with post-poliomyelitis syndrome and electromechanical function in myotonic dystrophy (level C rating, class III data).

Assessment of disease progression in motor neuron disease.

Motor neuron disease (MND) is characterised by progressive deterioration of the corticospinal tract, brainstem, and anterior horn cells of the spinal cord. There is no pathognomonic test for the diagnosis of MND, and physicians rely on clinical criteria-upper and lower motor neuron signs-for diagnosis. The presentations, clinical phenotypes, and outcomes of MND are diverse and have not been combined into a marker of disease progression. No single algorithm combines the findings of functional assessments and rating scales, such as those that assess quality of life, with biological markers of disease activity and findings from imaging and neurophysiological assessments. Here, we critically appraise developments in each of these areas and discuss the potential of such measures to be included in the future assessment of disease progression in patients with MND.