Autonomic cardiovascular responses in antecedent poliomyelitis

Autonomically mediated cardiovascular responses were evaluated in 20 subjects with antecedent poliomyelitis and compared to data from an age- and sex-matched control group. The polio subjects had a lower heart rate response to the Valsalva manoeuvre but the same respiratory sinus arrhythmia as the controls. From this it is concluded that the polio subjects had a normal vagal function. The polio subjects had a greater initial heart rate increase but the same blood pressure response to the orthostatic position as the controls. This indicates a normal function of the sympathetic nerves. The greater heart rate increase is most likely caused by a displacement of blood to the legs because of muscle atrophy. The polio subjects had a smaller blood flow increase as an initial response to an isometric handgrip than the controls. This might be attributed to a reduced beta-adrenergic vasodilation, possibly due to a reduced central vasomotor drive. It is concluded that subjects with antecedent poliomyelitis have no significant dysfunction of the peripheral autonomic nerves. Thus, there is no deterioration of the peripheral autonomic nerve function in parallel with the progressive muscle atrophy and paralysis earlier described in post-polio subjects.     

Autonomic cardiovascular responses in distal myopathy (Welander)

Autonomically mediated cardiovascular responses were evaluated in 9 patients with Welander distal myopathy and compared to data from an age- and sex-matched control group. The myopathy patients had a normal respiratory sinus arrhythmia and a normal heart rate response to the Valsalva menoeuvre, indicating a normal vagal function. They had a normal initial heart rate response to the orthostatic position, indicating a normal function of the sympathetic nerves. The main difference between the groups was found in the orthostatic position. The myopathy patients reacted with a greater increase in systolic blood pressure and a smaller heart rate increase than the controls. This suggests an altered peripheral vasomotor function, possibly with a more predominant activation of alfa than beta adrenergic receptors leading to vasoconstriction. In addition, a low forearm blood flow at rest and a les pronounced blood flow increase during the isometric handgrip were found in the myopathy patients. This finding could also be explained by proneness to vasoconstriction. It is concluded that patients with Welander distal myopathy have no signs of dysfunction of the peripheral autonomic nerves.     

Autonomic cardiovascular responses in parkinsonism: effect of levodopa with dopa-decarboxylase inhibition

ABSTRACT – Autonomically mediated cardiovascular responses to certain manoeuvres were studied in 20 parkinson patients, 24 h off levodopa-decarboxylase inhibitor medication and again one h after medication. Results were compared with 15 healthy control subjects. The heart rate at rest was higher in parkinson, the respiratory sinus arrhythmia was lower, while the Valsalva ratio, the heart rate and blood pressure responses during an orthostatic test and the heart rate response to a dive reflex test were normal. These findings indicate a normal function of peripheral autonomic nerves and a possible central parasympathetic dysfunction.
There were significantly attenuated responses of heart rate, blood pressure and contralateral forearm blood flow to an isometric handgrip. Since the peripheral autonomic nerves seemed to be normal, these results could be related to a reduced central command and/or diminished stimulation of postulated peripheral ergoreceptors in parkinsonism.
There was no major effect on the cardiovascular responses by the acutely administered medication.     

Sympathetic iris function in amyotrophic lateral sclerosis

Summary Autonomic fibres are generally regarded as being spared in amyotrophic lateral sclerosis. Anatomical studies have cast some doubt upon this hypothesis. The present study describes the pupillary responses to tyramine, a norepinephrine releaser, and to phenylephrine, a directly acting sympathomimetic, in 11 patients with ALS and matched controls. Patients and controls showed a similar sensitivity to sympathomimetic agents, and our results lend some support to the hypothesis that sympathetic functions are not involved in ALS.     

Respiratory function in amyotrophic lateral sclerosis

Abstract. The aim of this study was to examine the vital capacity (FVC) and forced expiratory volume in 1 s (FEV 1) in relation to the site of amyotrophic lateral sclerosis (ALS) onset and the duration of the disease. Respiratory involvement is the principal cause of death in ALS patients. The study was conducted at the Department of Neurology, University School of Medicine in Lublin. The study comprised 18 ALS patients. The average duration of ALS was 12 months. The patients were divided into two groups according to the site of ALS onset and into two groups according to the duration of the disease. FVC was significantly higher in the group of patients with a limb onset than in the group of patients with a bulbar onset of the disease. The study has shown respiratory function disturbances in ALS patients. FVC significantly depends on the site of ALS onset but not on the duration of the disease.     

Alteration in autonomic function and cardiovascular regulation in amyotrophic lateral sclerosis

Summary Autonomic function mediating cardiovascular regulation was evaluated in amyotrophic lateral sclerosis (ALS) in comparison with Shy-Drager syndrome. The subjects were 14 normal controls and 9 patients each with ALS and Shy-Drager syndrome. To evaluate the autonomic function in detail, a new series of quantitative autonomic function tests was conducted, in conjunction with conventional tests. In patients with ALS, the data indicated subclinical sympathetic hyperfunction and parasympathetic (vagal) hypofunction, probably resulting in cardiovascular dysfunction.     

Minocycline in amyotrophic lateral sclerosis: a pilot study

Abstract Recent studies indicate that minocycline exerts neuroprotective effects in vitro and in vivo, and suggest that the drug may represent a novel therapeutic approach to amyotrophic lateral sclerosis (ALS). In this study we investigated the safety of combined treatment with minocycline and riluzole in ALS. Twenty ALS patients were randomised into two groups and administered either riluzole (50 mg b.i.d.) or riluzole and minocycline (100 mg i.d.) for 6 months. Disease progression was measured by means of the ALS-Functional Rating Scale score at monthly intervals. Respiratory function was measured at the beginning of the study and repeated after 3 and 6 months of treatment. Combined treatment with minocycline and riluzole was not followed by significant side effects. This pilot study shows that minocycline and riluzole can be taken safely together. Further trials are needed to assess efficacy of such treatment.     

Sympathetic skin response in amyotrophic lateral sclerosis

Objectives– The aim of our study was to verify the usefulness of the sympathetic skin response (SSR) as an instrument for assessing autonomic involvement in amyotrophic lateral sclerosis (ALS). Material and methods– We studied palmar and plantar SSR in 31 patients with ALS (mean age: 58.4±9.3 years); 48 age-matched healthy subjects constituted the control group. Results– Palmar SSR was elicitable in all patients, and its latency and amplitude did not significantly differ from that of the controls. Plantar response was evoked in all but 7 patients. The lack of response was significantly related to the functional disability and duration of the disease. Conclusions– We conclude that SSR, even the plantar response, cannot be considered a useful tool for detecting early autonomic involvement in ALS.     

Sympathetic cholinergic dysfunction in amyotrophic lateral sclerosis

The results of evaluation of the autonomic nervous system of a patient with amyotrophic lateral sclerosis are presented. As previously reported, parasympathetic function and sympathetic adrenergic function were normal as assessed by cardiovascular reflexes. However, a disturbance in sympathetic cholinergic function as measured by the sympathetic skin response was demonstrated. We suggest that the latter test be included in all electrophysiological evaluations of autonomic function in amyotrophic lateral sclerosis.     

Autonomic system and amyotrophic lateral sclerosis

Introduction: The aim of this study is to characterize autonomic impairment in motor neuron disease. Methods: Neurological evaluations and autonomic testing were analyzed retrospectively in 132 patients: 86 classic amyotrophic lateral sclerosis (ALS), 36 lower motor neuron (LMN), and 10 upper motor neuron (UMN) predominant disease. Results: One‐third of patients were symptomatic; urinary urgency and constipation were the most frequent symptoms. Increased Composite Autonomic Severity Score (CASS) was present in 75% with mild impairment (CASS 1–3) in 85% and moderate (CASS 4–7) in 15%. The frequencies of testing abnormalities were: sudomotor 46%, cardiovagal 50%, and adrenergic 14%. The UMN group had significantly higher median CASS scores than the classic ALS (P = 0.021) and LMN group (P = 0.018). Conclusions: We found predominantly mild autonomic impairment in ALS patients, with mostly cardiovagal and sudomotor involvement. Moderate autonomic failure occurred in 1 of 7 patients, especially those with an UMN presentation. Patients with selective corticospinal tract involvement may have more impairment of autonomic pathways. Muscle Nerve 51 :676–679, 2015     

Value of spirometric investigations in amyotrophic lateral sclerosis

The respiratory function has been studied in 37 patients with ALS. 15 of them (5 till death) were followed with serial spirometric tests. The data, as a whole, show a diminution of vital capacity, a diminution of forced expiratory volume per second, an increase of the residual volume and of the Motley index; blood gas analysis showed no significant alterations apart from slight hypoxemia. Patients with bulbar ALS presented marked abnormalities of the spirometric and blood gas analysis parameters. In the cases followed with serial spirometric tests VC, Motley index and FEV ₁ gradually deteriorated as the disease advanced. In the deceased patients a sudden and serious aggravation of these values occurred. This was especially true for FEV ₁ and Motley index during the 3 months preceding death. The variations in residual volume were less indicative. Finally, the influence of smoking and of pulmonary and bronchial pathology, present or past, was not significant.

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Sommario Prove di funzionalità respiratoria sono state eseguite in 37pazienti con Sclerosi Laterale Amiotrofica; 15 casi sono stati seguiti con spirometrie seriate e di questi 5 fino al momento del decesso. I risultati evidenziano una diminuzione della capacità vitale (CV) e del volume espiratorio massimo al secondo (FEV ₁ ) un aumento del volume residuo (VR) e dell'indice di Motley;l'emogasanalisi non ha dimostrato modificazioni significative fatta eccezione per una lieve ipossiemia.I pazienti con SLA di tipo bulbare hanno mostrato una compromissione più marcata dei parametri spirometrici ed emogasanalitici. Nei casi seguiti con spirometrie seriate si è osservato un graduale peggioramento della CV, del FEV ₁ e dell'indice di Motley lungo il discorso della malattia. Nei pazienti deceduti si è riscontrato un brusco e netto peggioramento di questi parametri ed in particolare del FEV ₁ e dell'indice di Motley nei tre mesi che avevano preceduto la morte. Lo stato di fumatore e la patologia polmonare in atto o pregressa non hanno mostrato incidenze sinificative.

     

Assessment of sympathetic sudomotor function in amyotrophic lateral sclerosis with electrochemical skin conductance

ObjectiveAmyotrophic lateral sclerosis (ALS) is now recognized as a multisystem neurodegenerative disorder, comprising autonomic dysfunction. We aimed to assess sudomotor function in ALS by measuring the electrochemical skin conductance (ESC).MethodsThirty-one ALS patients [median age of 62 years (1st-3rd interquartile range – IQR, 56–72), male 71%] were prospectively compared with 29 healthy controls, matched for age and sex. We analysed ESC results from hands and feet, bilaterally.ResultsA total of 120 ESC recordings were obtained. Hands and feet ESC measurements were significantly lower in patients compared with controls [64 μS (1st-3rd IQR, 57–58) versus 78 μS (1st-3rd IQR, 70.5–84), p < 0.001 and 76 μS (1st-3rd IQR, 68–83) versus 81 μS (1st-3rd IQR, 78–86), p = 0.008, respectively]. In ALS group, no differences were observed between spinal and bulbar-onset forms for hands and feet results (p > 0.05). Hands and feet ESC measurements did not correlate also with disease duration, total ALSFRS-R scale, or ALSFRS-R progression rate (all p > 0.05).ConclusionESC is a non-invasive, fast and quantitative method suitable for assessing sudomotor function. ALS patients revealed a decreased function in upper and lower extremities.SignificanceSudomotor dysfunction is part of the ALS manifestations.     

Three cases of amyotrophic lateral sclerosis in a common occupational environment

Summary Three unrelated school teachers taught in the same school classroom for 2–5 years and subsequently developed amyotrophic lateral sclerosis (ALS) over an 18-year period. This clustering was not accompanied by an increased death rate for ALS in the county where the teachers lived and worked. Statistical analysis revealed that ALS as the cause of death for three teachers from the same school would be highly improbable as a random event. These findings suggest that the patient's shared school environment may have been a source of exposure to an agent pathogenetically significant in the development of their disease.     

Autonomic involvement in multiple sclerosis: a pupillometric study

To study pupillary autonomic function in multiple sclerosis (MS), we examined 36 subjects with low disability, preserved visual acuity and no recent history (2 years) of optic neuritis or actual visual complaints. Compared to controls, MS patients showed a greater dilatator reaction with darkness and, for the light reflex, a lower amplitude and contraction rate and a greater recovery of pupillary diameter 5 s after the stimulus. Within the MS group, no difference was found comparing patients with or without the following characteristics: nuclear magnetic resonance imaging evidence of midbrain lesions; increased visual evoked potential P100 latency; and a previous history of optic neuritis. No correlation was found between P100 latency, duration of disease and pupillometric parameters. Our results indicate that in MS patients there is autonomic dysfunction with a reduction of parasympathetic tone and a relative increase in sympathetic dilatator tone to the pupils. We suggest that pupillary abnormalities could be due to non-specific impairment of the central pathways subserving pupil functions.     

The physician-patient relationship in amyotrophic lateral sclerosis

The principal models of the physician-patient relationship are analysed in terms of their historical development. An outline is given of the clinical, psychological and ethical particularities of the approach to patients with amyotrophic lateral sclerosis. The peculiarities of this disease are so exclusive that they do not resemble other progressive diseases with a negative prognosis, and therefore require an equally exclusive approach to the physician-patient relationship. This approach should not only be informative, scientific and interpretative-deliberative, but most simultaneously be founded on a solid therapeutic alliance aimed at seeking the best interests of the patients while respecting their autonomy as well as their “good” (not only in the sense of physical well-being, but also in terms of respect for their personal values). This is the only way to confront the conflicts that inevitably arise (especially in advanced stages of the disease) without the risks associated with a desire to escape or to adopt extreme solutions (such as euthanasia and therapeutic insistence) and without the risk of burn-out. Received: 5 May 2000 / Accepted in revised form: 6 December 2000     

Muscular mitochondrial function in amyotrophic lateral sclerosis is progressively altered as the disease develops: a temporal study in man

We performed repeated analysis of mitochondrial respiratory function in skeletal muscle (SM) of patients with early-stage sporadic amyotrophic lateral sclerosis (SALS) to determine whether mitochondrial function was altered as the disease advanced. SM biopsies were obtained from 7 patients with newly diagnosed SALS, the same 7 patients 3 months later, and 7 sedentary controls. Muscle fibers were permeabilized with saponin, then skinned and placed in an oxygraphic chamber to measure basal and maximal adenosine diphosphate (ADP)-stimulated respiration rates and to assess mitochondrial regulation by ADP. We found that the maximal oxidative phosphorylation capacity of muscular mitochondria significantly increased, and muscular mitochondrial respiratory complex IV activity significantly decreased as the disease advanced. This temporal study demonstrates for the first time that mitochondrial function in SM in human SALS is progressively altered as the disease develops.     

Decreased heart rate variability in amyotrophic lateral sclerosis

Autoregressive spectral analysis of heart rate variability (HRV) was performed in 29 patients with amyotrophic lateral sclerosis (ALS) and 33 age-matched healthy subjects to evaluate the involvement of the autonomic nervous system. HRV analysis provides a means to recognize low (LF) and high (HF) frequency components, respectively mediated by sympathetic and parasympathetic heart control. An increase in the mean heart rate at rest (P < 0.001), a decrease in standard deviation of R-R interval as well as in PNN50 (P < 0.001), and an increase in the LF/HF component ratio (P < 0.01) were found in the ALS patients, indicating a vagal–sympathetic imbalance. These alterations were not related to the clinical features and to the duration of the disease. Our results suggest a subclinical involvement of the autonomic nervous system in ALS, particularly affecting parasympathetic cardiovascular control. © John Wiley & Sons, Inc.     

肌萎缩性侧索硬化症患者体感诱发电位研究

目的 研究肌萎缩性侧索硬化症(ALS)患者体感诱发电位(SEP)变化。方法 采用正中神经及肠后神经体感诱发电位(mSEP、tSEP)对30例患者进行检测，并与27例健康人作对比。结果 mSEP和tSEP的异常率分别为43．3％(13／30)及28％(7/5)，除N9、PF(腘点)、LP(T12点)峰潜伏期和对照组相比无显著差异外，其余各峰潜伏期及峰间期和对照组相比均有显著性差异。结论 ALS患者存在感觉通路损害，且中枢的改变较周围更明显，SEP检查对患者感觉损害的定位有一定价值。     

Creatine kinase activity in amyotrophic lateral sclerosis patients

Abstract. The aim of this study was to investigate creatine kinase (CK) in the serum of amyotrophic lateral sclerosis (ALS) patients. Previous investigations have shown an increased CK activity in ALS patients and this has been suggested to be an indicator of patients survival. The study was conducted at the Department of Neurology, University School of Medicine in Lublin. Thirty ALS patients took part in the study. The average duration of the disease was 17 months. Serum CK levels were measured by the enzymatic method with N-acethylcysteine. CK was elevated in 43.3% of the ALS patients. There were no significant differences in the serum CK level between the groups of the ALS patients depending on age, sex, duration of the disease, or clinical condition of patients. The CK level was significantly higher in the serum of the patients with a limb onset than in patients with a bulbar onset of ALS. Our study confirmed the increase in the serum CK activity in ALS patients. CK activity depends on a limb onset or a bulbar onset of ALS, but not on the duration of the disease and the severity of the clinical condition.     

Novel drug development for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) has become an increasingly attractive area for the pharmaceutical industry, the most experimentally tractable of the neurodegenerative diseases. Mechanisms underlying cell death in ALS are likely to be important in more common but more complex disorders. Riluzole, the only drug launched for treatment ALS is currently undergoing industrial trials for Alzheimer’s, Parkinson’s, Huntington disease, stroke and head injury. Other compounds in Phase III testing for ALS (mecamserin, xaliproden, gabapentin) are also in trials for other neurodegenerative disorders. Mechanisms of action of these advanced compounds are limited to glutamate antagonism, direct or indirect growth factor activity, as well as GABA agonism and interaction with calcium channels. A broader range of mechanisms is represented by compounds in Phase I trials: glutamate antagonism (dextramethorphan/p450 inhibitor; talampanel), growth factors (leukemia inhibiting factor; IL-1 receptor; encapsulated cells secreting CNTF) and antioxidants (TR500, a glutathione-repleting agent; recombinant superoxide dismutase; procysteine.) An even broader range of mechanisms is being explored in preclinical discovery programs. Recognition of the difficulties associated with delivery of protein therapeutics to the CNS has led to development of small molecules interacting either with neurotrophin receptors or with downstream intracellular signalling pathways. Other novel drug targets include caspaces, protein kinases and other molecules influencing apoptosis. High-throughput screens of large libraries of small molecules yield lead compounds that are subsequently optimized by chemists, screened for toxicity, and validated before a candidate is selected for clinical trials. The net is cast wide in early discovery efforts, only about 1% of which result in useful drugs at the end of a decade-long process. Successful discovery and development of novel drugs will increasingly depend on collaborative efforts between the academy and industry.