INTRINSIC MOTOR NEURONE EXCITABILITY IS REDUCED IN SOLEUS AND TIBIALIS ANTERIOR OF OLDER ADULTS

Age-related deterioration within both motor neurones and monoaminergic systems should theoretically reduce neuromodulation by weakening motor neuronal persistent inward current (PIC) strength. However, this assumption remains untested. Surface electromyographic signals were collected using two 32-channel electrode matrices placed on soleus and tibialis anterior of 25 older adults (70±4years) and 17 young adults (29±5 years) to investigate motor unit discharge behaviours. Participants performed triangular-shaped plantar and dorsiflexion contractions to 20% of maximum torque at a rise-decline rate of 2%/s of each participant's maximal torque. Pairwise and composite paired-motor unit analyses were adopted to calculate delta frequency (ΔF) and estimate PIC amplitudes. ΔF has been used to differentiate between the effects of synaptic excitation and intrinsic motor neuronal properties and is assumed to be proportional to PIC amplitude. The results show that soleus and tibialis anterior motor units in older adults had lower ΔFs when calculated with the pairwise (-0.99 and -1.29 pps, respectively) or composite (-1.65 and -2.26 pps, respectively) methods. Older adults' motor units discharged at lower rates (-2.14 and -2.03 pps, respectively) and were recruited at lower torque levels (-1.50 and -2.06% of maximum, respectively) than young adults. These results demonstrate reduced intrinsic motor neurone excitability during low-force contractions in older adults, likely mediated by decreases in the strength of persistent inward currents. Our findings might be explained by deterioration in the motor neurones or monoaminergic systems, and could contribute to the decline in motor function during ageing; these assumptions should be explicitly tested in future investigations.

Involuntary sustained firing of plantar flexor motor neurones: effect of electrical stimulation parameters during tendon vibration

Purpose Simultaneous application of tendon vibration and neuromuscular electrical stimulation (NMES) induces an involuntary sustained torque. We examined the effect of different NMES parameters (intensity, pattern of stimulation and pulse width) on the magnitude of the evoked involuntary torque. Methods Plantar flexor torque was recorded during 33-s Achilles tendon vibration with simultaneous 20-Hz NMES bouts on triceps surae (n = 20; 13 women). Intensity was set to elicit 10, 20 or 30% of maximal voluntary contraction torque (MVC), pulse width was narrow (0.2 ms) or wide (1 ms), and the stimulus pattern varied (5 × 2-s or 10 × 1-s). Up to 12 different trials were performed in a randomized order, and then repeated in those who produced a sustained involuntary torque after the cessation of vibration. Results Six of 7 men and 5 of 13 women produced a post-vibration sustained torque. Eight of 20 participants did not complete the 30% trials, as they were perceived as painful. Torque during vibration at the end of NMES and the increase in torque throughout the trial were significantly higher in 20 than 10% trials (n = 11; 9.7 ± 9.0 vs 7.1 ± 6.1% MVC and 4.3 ± 4.5 vs 3.6 ± 3.5% MVC, respectively). Post-vibration sustained torque was higher in wide pulse-width trials (5.4 ± 5.9 vs 4.1 ± 4.3% MVC). Measures of involuntary torque were not different between 20 and 30% trials (n = 8). Conclusion Bouts of 5 × 2-s NMES with wide pulse width eliciting 20% MVC provides the most robust responses and could be used to maximise the production of involuntary torque in triceps surae.

Motor neurone disease

Motor neurone disease describes a group of rare, fatal, neurodegenerative disorders. They are devastating conditions that cause the loss of upper and/or lower motor neurones, leading to a variety of progressive neurological symptoms that can develop over months to years. Due to the rarity of these conditions and the differing and often insidious symptoms there is typically a prolonged delay between presentation and diagnosis of between 15 and 18 months on average. There is often a short prognosis of 3 years, though this can vary significantly depending on the type of syndrome diagnosed. Primary care clinicians play a key role in both facilitating early diagnosis and subsequent management and co-ordination of care in the community.

Finger extension weakness and downbeat nystagmus motor neurone disease (FEWDON-MND)

Atypical motor neurone disease (MND) represents a challenging and expanding group of neurodegenerative disorders involving the upper or lower motor neurones, and rarely both. Neuro-ophthalmological disturbances such as gaze-evoked downbeat nystagmus are extremely rare in the context of typical and atypical MND. Finger extension weakness and downbeat nystagmus motor neurone disease (FEWDON-MND) syndrome has been recently recognised as a distinct syndromic phenotype of MND, with a characteristic clinical picture. We describe a 63-year-old woman with long-standing lower motor neurone involvement of the upper limbs, who on examination had gaze-evoked downbeat nystagmus. After extensive negative investigation for secondary causes of MND and downbeat nystagmus, we diagnosed FEWDON-MND syndrome.

Acute onset of bulbar amyotrophic lateral sclerosis after flu – look at the differential diagnosis: A case report

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting upper and lower motor neurones. It can be either familial (fALS) or sporadic (sALS). ALS is characterized by muscle weakness and atrophy that can involve the limbs and trunk (i.e. the spinal form of the disease) or speech and swallowing (i.e. the bulbar form). The aetiology of sALS remains unclear although a gene–environment interaction has been proposed as a concomitant trigger for the neurodegenerative process together with viral infections, smoking, heavy metals and pesticide exposure. Herein, we report the case of a 67-year-old woman who experienced an acute onset of bulbar ALS with an atypical clinical course that was probably triggered by a bout of influenza.

Neurochondrin interacts with the SMN protein suggesting a novel mechanism for Spinal Muscular Atrophy pathology

Spinal Muscular Atrophy (SMA) is an inherited neurodegenerative condition caused by reduction in functional Survival Motor Neurones Protein (SMN). SMN has been implicated in transport of mRNA in neural cells for local translation. We previously identified microtubule-dependant mobile vesicles rich in SMN and the splicing factor SmB, a member of the Sm protein family, in neural cells. By comparing the proteome of SmB to that of SmN, a neural-specific Sm protein, we now show that the essential neural protein neurochondrin (NCDN) interacts with Sm proteins and SMN in the context of mobile vesicles in neurites. NCDN has roles in protein localisation in neural cells, and in maintenance of cell polarity. NCDN is required for the correct localisation of SMN, suggesting they may both be required for formation and transport of trafficking vesicles. NCDN provides a potential therapeutic target for SMA together with, or in place of, those targeting SMN expression.

Neurological emergencies

A number of neurological conditions can present to the emergency department in a variety of presentations. This chapter summarizes the common neurological problems that may be examined in the Intermediate FRCEM short-answer question (SAQ) paper. This chapter includes the pathophysiology and management of an unconscious patient which may commonly appear in the SAQ paper. In addition, it also includes sections of epilepsy, headaches and strokes, and their subclassification and diagnosis. Many individuals find the differentiation of the cause of motor weakness complicated. This chapter summarizes the different causes of motor weakness, in terms of upper and lower motor neurones lesions and the clinical features associated to aid diagnosis. There is also a section on spinal cord pathology and hydrocephalus knowledge of which is essential for the SAQ paper.

Facial Onset Sensory and Motor Neuronopathy: Further Evidence for a TDP-43 Proteinopathy

Three patients with the clinical and investigation features of facial onset sensory and motor neuronopathy (FOSMN) syndrome are presented, one of whom came to a post-mortem examination. This showed TDP-43-positive inclusions in the bulbar and spinal motor neurones as well as in the trigeminal nerve nuclei, consistent with a neurodegenerative pathogenesis. These data support the idea that at least some FOSMN cases fall within the spectrum of the TDP-43 proteinopathies, and represent a focal form of this pathology.