Non-Pharmacological Interventions on Pain in Amyotrophic Lateral Sclerosis Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting upper and lower motor neurons. Some ALS patients exhibit concomitant nonmotor signs; thus, ALS is considered a multisystemic disorder. Pain is an important nonmotor symptom. Observational and case-control studies report high frequency of pain in ALS patients and it has been correlated with depression and quality of life. There are no specific scales for the assessment of pain and no randomized controlled trials (RCTs) regarding the drug management of pain in ALS. AIM: To systematically review the evidence for the nonpharmacological interventions (NPIs) in relieving pain in ALS, on March 2024, we searched the following databases: Pubmed, Scopus, Web of Science, and Cochrane. We also checked the bibliographies of trials identified to include further published or unpublished trials. MAIN RESULTS: A total of 1003 records were identified. Finally, five RCTs including 131 patients (64 in the intervention group and 67 in the control group) were included for meta-analysis. The interventions of the included RCTs consisted of muscle exercise, combined aerobics-strength intervention, and osteopathic manual treatment. The meta-analysis did not find a statistically significant difference in favor of NPIs for alleviating pain in ALS patients. CONCLUSIONS: ALS has a fulminant course and irreversibly leads to death. Pain in ALS patients, although a common nonmotor symptom, is often unrecognized and undertreated, and this is underlined by the lack of any RCTs on drug therapy for pain. Albeit NPIs are considered safe, as adverse effects are rarely reported, this systematic review did not provide sufficient evidence for a beneficial effect on pain. The scarceness of relevant literature highlights the need for future studies, with larger samples, more homogeneous in terms of interventions and population characteristics (stage of disease), and better choice of measurement scales to further investigate the efficacy, if any, of various pain interventions in ALS patients.

Autonomic dysfunction in amyotrophic lateral sclerosis: A neurophysiological and neurosonology study.

BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting upper and lower motor neurons. Some ALS patients exhibit concomitant nonmotor signs, and thus ALS is considered a multisystem disorder. The aim of this study is to investigate autonomous nervous system involvement in ALS. METHODS: We investigated 21 ALS patients and 28 age-matched controls. ALS patients were assessed for disease severity with the Revised-ALS Functional Rating Scale (ALSFSR) and for the presence of autonomic symptoms with the Composite Autonomic Symptom Score scale. Sympathetic nervous system was evaluated by sympathetic skin response (SSR) and parasympathetic nervous system by ultrasonography of vagus nerve (VN) at the level of the thyroid gland. RESULTS: SSR latencies were shorter and SSR amplitudes were higher in controls compared to ALS patients. The cross-sectional area (CSA) of the VN was significantly smaller in ALS patients (mean CSA right/left: 1.73±0.62 mm2 /1.47±0.53 mm2 ) compared to controls (mean CSA right/left: 2.91±0.79 mm2 /2.30±0.80 mm2 ), right: p <. 001, left: p <. 001. There was a significant negative correlation between disease duration and CSA of left-VN (r = -0.493, p = .023). This correlation was attenuated between disease duration and CSA of right-VN (r = -0.419, p = .059). ALSFSR-R was positively correlated to CSA of right-VN (p = .006, r = 0.590). CSA of VN did not correlate with bulbar involvement. CONCLUSIONS: This study confirms the presence of autonomic dysfunction in ALS patients and provides evidence of VN atrophy that correlates with disease severity and duration and is independent of bulbar involvement. Degeneration of dorsal nucleus neurons of the VN is hypothesized.

Neurophysiological and ultrasonographic comparative study of autonomous nervous system in patients suffering from fibromyalgia and generalized anxiety disorder.

BACKGROUND: Fibromyalgia (FM) and generalized anxiety disorder (GAD) share common clinical features: they both affect women more than men, their diagnosis is based solely on clinical criteria, and some of the symptoms such as anxiety, aches and muscle tension, sleep disorders, and cognitive dysfunction occur in both diseases. For both conditions, an underlying dysregulation of the autonomic nervous system (ANS) has been proposed. OBJECTIVE: The aims of this study were to investigate ANS dysfunction in FM and GAD and compare them with controls. METHODS: Sympathetic skin response (SSR) from palm and sole and cross-sectional area (CSA) of bilateral vagus nerves (VN) were measured in 28 healthy controls, 21 FM patients, and 24 GAD patients. RESULTS: CSA of VN was significantly smaller in FM patients (right: 1.97 ± 0.74mm2, left: 1.75 ± 0.65 mm2) and GAD patients (right: 2.12 ± 0.97mm2, left: 1.71 ± 0.86 mm2) compared to controls (right: 3.21 ± 0.75 mm2, left: 2.65 ± 1.13 mm2, p < 0.001, but did not differ between the two patient groups. SSR parameters were similar between patients and controls. SSR latency correlated to clinical scales (FM Widespread Pain Index) in the FM group (r = 0.515, p = 0.02 and r = 0.447, p = 0.05) for the upper and lower limbs respectively, but no other correlation between clinical and neurophysiological parameters was identified. CONCLUSION: This study confirms similar ANS abnormalities in FM and GAD that fairly distinguish them from controls and support the hypothesis of a common pathophysiological substrate underlying both conditions.

Neurobrucellosis presenting as clinically definite amyotrophic lateral sclerosis.

Purpose/Aim: We describe the first case of a patient with neurobrucellosis presenting with clinically-definite ALS. MATERIAL AND METHODS: A 48-year old male patient, in whom the diagnoses of systemic brucellosis and clinically definite ALS were undoubtedly confirmed and were eventually causally interrelated. The disease-specific antibiotic therapy was unsuccessful to slow the evolution of the motor neuron disease and the patient became non ambulatory over time. RESULTS: Considering the close temporal association of ALS onset with the systemic Brucella infection and consequent antigenic stimuli, we might suggest that human brucellosis might have triggered a process of motor neuron degeneration in keeping with neurobrucellosis, primarily due to parainfectious mechanism. CONCLUSION: Our case helps to shed light on the factors that may trigger or only fasten motor neuron disease manifestations.

Impaired interhemispheric inhibition in amyotrophic lateral sclerosis.

The pathogenesis of sporadic amyotrophic lateral sclerosis (ALS) remains unknown. Neurophysiological studies provide evidence of hyperexcitability of the motor cortex or of impairment of inhibitory intrahemispheric modulation of the corticomotoneuron in ALS. In this paper, we used TMS to elicit transcallosal inhibition of the motor cortex in ALS patients in order to investigate whether interhemispheric inhibitory mechanisms subserved by callosal fibres are also disturbed in ALS. Twenty-five patients with ALS and 18 controls were recruited for the study. Resting Motor Threshold (RMT), Silent Period (SP) and interhemispheric inhibition (IHI) were recorded. No significant difference was detected regarding RMT or the duration of SP between patients and controls. IHI was detected in all controls. IHI was totally absent in eight patients, in another eight patients IHI did not reach a significant level and in the remaining nine patients was normal. The degree of IHI was significantly lower in ALS patients than in controls (p = 0.001). In conclusion, altered IHI in ALS patients is in line with the general pattern of reduced corticomotoneuron inhibition, being thus, one of the factors which may lead to chronic overexcitation of pyramidal cells.

Intraoperative radial nerve injury during coronary artery surgery--report of two cases.

BACKGROUND: Peripheral nerve injury and brachial plexopathy are known, though rare complications of coronary artery surgery. The ulnar nerve is most frequently affected, whereas radial nerve lesions are much less common accounting for only 3% of such intraoperative injuries. CASE PRESENTATIONS: Two 52- and 50-year-old men underwent coronary artery surgery. On the first postoperative day they both complained of wrist drop on the left. Neurological examination revealed a paresis of the wrist and finger extensor muscles (0/5), and the brachioradialis (4/5) with hypoaesthesia on the radial aspect of the dorsum of the left hand. Both biceps and triceps reflexes were normoactive, whereas the brachioradialis reflex was diminished on the left. Muscles innervated from the median and ulnar nerve, as well as all muscles above the elbow were unaffected. Electrophysiological studies were performed 3 weeks later, when muscle power of the affected muscles had already begun to improve. Nerve conduction studies and needle electromyography revealed a partial conduction block of the radial nerve along the spiral groove, motor axonal loss distal to the site of the lesion and moderate impairment in recruitment with fibrillation potentials in radial innervated muscles below the elbow and normal findings in triceps and deltoid. Electrophysiology data pointed towards a radial nerve injury in the spiral groove. We assume external compression as the causative factor. The only apparatus attached to the patients' left upper arm was the sternal retractor, used for dissection of the internal mammary artery. Both patients were overweight and lying on the operating table for a considerable time might have caused the compression of their left upper arm on the self retractor's supporting column which was fixed to the table rail 5 cm above the left elbow joint, in the site where the radial nerve is directly apposed to the humerus. CONCLUSION: Although very uncommon, external compression due to the use of a self retractor during coronary artery surgery can affect--especially in obese subjects--the radial nerve within the spiral groove leading to paresis and should therefore be included in the list of possible mechanisms of radial nerve injury.

Thyroid function in patients with Alzheimer disease: implications on response to anticholinesterase treatment.

Increasing evidence supports an extensive interrelationship between thyroid hormones and the cholinergic system, which is selectively and early affected in Alzheimer disease (AD). The aim of the present study was to explore thyroid function in patients with AD before and after acetylcholinesterase inhibition treatment to possibly identify variances in response. Thyroid function tests were evaluated in 28 AD patients and 24 age and sex-matched controls. Nineteen of the patients were reevaluated after (4 mo) treatment with donepezil. Serum thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4), the free fractions (fT3, fT4) and thyroid autoantibodies were determined using standard methods. All subjects were clinically euthyroid. Patients presented with higher fT4 and anti-thyroperoxidase levels, as compared with the controls. Significant reduction in T4, fT3, fT4, and anti-thyroperoxidase levels were observed 4 months after treatment. Responders had higher T4 and fT4, than nonresponders, followed by significant reductions after treatment. The above, within the normal range alterations, may represent a direct effect on hormone release from the thyroid gland and/or increased conversion of T4 to T3 within the brain. Higher T4 and fT4 levels before treatment might predict a favorable response to donepezil treatment.

Juvenile spring eruption: clinicopathologic features and phototesting results in 4 cases.

Juvenile spring eruption is a distinct photodermatosis characterized by the development of papules and vesicles on light-exposed areas of the ears usually in the early springtime. It primarily affects boys and young men, and has a tendency to occur in the form of small epidemics. We report a similar outbreak in separate groups of soldiers who were performing military exercises during cold and sunny weather of a midwinter season. The clinicopathologic features and phototesting results are described in 4 of these cases. All patients showed normal erythemal responses to monochromator phototesting with UV and visible wave bands. Photoprovative testing with repeated daily exposures of the ears to a broadband UVA source provoked diffuse erythema and itching in 1 case, whereas similar photoprovocation of a nonaffected area, ie, the flexor surface of the forearm, in 2 patients did not yield a skin reaction. Although the cause of juvenile spring eruption is not known, our observations further strengthen the hypothesis that the disorder is a localized variant of polymorphous light eruption.