Ocular fixation instabilities in motor neurone disease

Objective   Eye movements are classically felt to be spared in motor neurone disease (MND). Although a range of ocular motor disorders have been reported, no consistent pattern has been established. Disturbances of ocular fixation have been noted in MND; however, fixation has not yet been formally examined. With the recent characterization of ocular fixation using saccadic intrusion amplitude and fixation periods, we performed a cross-sectional study to examine for abnormalities of ocular fixation in non-dementing patients with MND. Methods   A total of 44 patients and 45 controls were recruited. Fixation was examined using infra-red oculography and all subjects then underwent a neuropsychological evaluation. Results   Saccadic intrusion amplitude was found to be greater in patients compared to controls and in particular, spinal-onset patients. Saccadic intrusion amplitude in patients correlated with neuropsychological measures sensitive to lesions of the frontal lobes. Conclusions   This is the first study to identify abnormalities of fixation in MND and these results indicate that ocular fixation instabilities may be a marker of the sub-clinical frontal lobe dysfunction in MND. A longitudinal study to examine if saccadic intrusion amplitude deteriorates with time would be of interest as this could provide a quantifiable objective marker of disease progression.     

Patterns of mortality in patients with motor neurone disease

OBJECTIVE: Motor neurone disease (MND) is a rapidly fatal condition with survival of less than 4 years. Patients can deteriorate quickly in the preterminal stages resulting in inappropriate resuscitation or admission to intensive care units (ICU) or accident and emergency (A & E). MATERIAL AND METHODS: We looked at patterns of mortality with emphasis on the place of death. A retrospective study was performed of all patients attending an MND clinic, who had died within a 10-year period. RESULTS: Of 179 patients (63 female), 81 patients (45%) died at home, in a hospice or in a nursing home. Sixty-five patients (36%) died in hospital (11 in ICU or A & E). Nine of the latter were previously known to have MND and six admissions were probably avoidable. Most ward patients died of respiratory causes and were treated conservatively. CONCLUSION: The proportion of patients dying in A & E or ICU was small but could have been reduced further. A number of those who died on the wards could probably have been managed conservatively at home. Older patients and those with bulbar disease had a poorer prognosis.     

Pattern of involvement in the cervical segments in the early stage of motor neurone disease: A single fibre EMG study

The right and left biceps and first dorsal interosseous muscles of 22 patients with motor neurone disease were studied by single fibre EMG at the time of diagnosis. The mean duration of symptoms was 8.1 months. The fibre density was increased in 87 of the 88 muscles studied. In the first dorsal interosseous muscles the fibre density was increased similarly on both sides, but in the biceps muscles of normal strength the fibre density was more markedly increased on the left than on the right. These findings suggest that in the early stage of the disease certain motor unit pools in the spinal cord are preferentially affected.     

Rising mortality from motor neurone disease: an explanation

There is considerable debate about the increasing mortality from motor neurone disease (MND). However, examination of the relationship between increased life expectancy (through decreased general mortality) and increased mortality in both England and Wales and the United States indicates a close association between the two variables. Using a statistical model, defined sub-populations susceptible to MND can be identified in both countries. The size of such a sub-population has been estimated from the 1989 mortality data to be approximately 160 000 people in England and Wales. The proportion of this sub-population dying from MND has increased over the last 30 years, rather than, as previously, dying at an earlier age from other conditions. On this basis, deaths from MND are expected to increase by a further 20% in this sub-population between 1991-2021 because of continuing changes in life expectancy. MND is a condition made increasingly visible in mortality statistics through decreased general mortality, rather than one in which the underlying population at risk has substantially changed. Aetiological extrapolations from the data indicate that susceptibility to the disease is acquired early in life, and that it is unlikely, given the relative stability of the underlying sub-population, that either changed environmental circumstances or artifactual factors can account in themselves for the rise in mortality.     

A neuropsychological investigation of dementia in motor neurone disease (MND)

Different clinical criteria for diagnosing dementia were compared in a sample of 69 patients with motor neurone disease (MND). Participants’ performances on a computerised battery of neuropsychological tests were evaluated to assess the usefulness of these tests in predicting dementia in MND. The results indicated that when diagnostic criteria for frontotemporal (FTD) were used as part of a questionnaire method of diagnosing dementia the incidence of dementia in MND was considerably greater than traditional estimates suggest. Through a series of logistic and multiple regressions the results demonstrated that neuropsychological test performance related well to diagnostic classifications of dementia. MND patients with a clinical diagnosis of dementia were likely to demonstrate impaired new learning; poor working memory and planning; slowness in information processing and rigidity in thinking. These features, which are typical of cases of FTD, suggest that the dementia of MND is usefully characterised as a form of FTD. The finding that neuropsychological impairment correlated with behavioural features of dysexecutive impairment in daily living, indicates that the management focus in MND must be broadened to include cognitive/behavioural issues.     

Pattern of motor neurone disease in eastern India

A clinical study about the pattern of motor neurone disease in eastern India was carried out from July 1993 to June 1995 at Bangur Institute of Neurology, Calcutta and SSKM Hospital, Calcutta. A total of 110 cases were studied and they constituted 0.11 % of all neurological cases seen in the general OPD. Of 110 cases, amyotropic lateral sclerosis (ALS) constituted 43.6%, progressive muscular atrophy (PMA) 10.9%, post-polio progressive muscular atrophy (PPMA) 1.8%, spinal muscular atrophy (SMA) 20%, atypical form Madras pattern of MND (MMND) 0.9% and monomelic amyotrophy (MM A) 22.7% of cases. Disease is more common in males than females and average duration of symptoms before presentation varied from 1 to 12 months. Most of the patients were either agricultural labourers or manual workers in ALS variety whereas MMA variety was evenly distributed in both hard labourers and sedentary workers. Most of the patients in MMA and SMA groups presented before 30 years of age whereas ALS and PMA group presented after 30 years. Trauma was the commonest antecedent event in ALS and MMA followed by electrocution in the same two groups. Family history was found to be absent in SMA group though the disease is considered as a hereditary one. Weakness of the limbs and wasting of the muscles were common presenting symptoms and signs. Bulbar symptoms and signs were found only in the ALS group. EMG showed neurogenic pattern and mixed pattern in most of the patients in all groups. Only a few patients showed myopathic pattern. Neuroimaging study helped in exclusion of compressive lesion excepting two cases of MMA where lacetal hypertrophy was present. Monomelic amyotrophy, a special variety of motor neurone disease, is not rare in this part as compared to other parts of India and Asia.     

Classification and clinical features of motor neurone diseases and motor neuropathies in adults

The term motor neurone disease encompasses combined upper and lower motor neurone disorders (amyotrophic lateral sclerosis), pure lower motor neurone disorders (spinal muscular atrophies, multifocal motor neuropathies, post irradiation lumbosacral radiculopathy, post-polio syndrome, hereditary bulbar palsy) and pure upper motor neurone disorders (primary lateral sclerosis, hereditary spastic paraplegia, neurolathyrism, Konzo). The chief clinical and electrophysiological criteria for these different disorders are discussed, with particular attention to diagnostically distinctive characteristics of each. Age of onset, and inheritance are considered as additional diagnostic features. Received: 8 July 1998 Accepted: 23 July 1998     

Nerve conduction studies in upper limbs of patients with cervical spondylosis and motor neurone disease

Proximal conduction studies by F-wave technique, with conventional distal motor and sensory conduction were performed along the ulnar nerves of 20 patients each with cervical spondylotic radiculopathy and/or myelopathy and with classical motor neurone disease (MND). Such F-wave parameters as shortest F-latency, F-conduction velocity, conduction time and F-ratio were calculated. Twenty-five age- and sex-matched healthy volunteers acted as controls. Proximal slowing associated with sensory conduction abnormalities and normal distal motor conduction favored cervical spondylosis (CS). Distal slowing with a normal proximal motor and sensory conduction was associated with motor neurone disease.     

Cognitive change in motor neurone disease/amyotrophic lateral sclerosis (MND/ALS)

A motor neuronopathy complicating frontotemporal dementia (FTD) has been recognised and designated FTD/motor neurone disease (MND). FTD is characterised by profound character change and altered social conduct, and executive deficits, reflecting focal degeneration of the frontal and temporal neocortex. The motor neuronopathy comprises bulbar palsy and limb amyotrophy. The major histological change is typically of microvacuolation of the cerebral cortex, with atrophy of the bulbar neurones and anterior horn cells of the spinal cord. Ubiquitinated inclusion bodies occur in large pyramidal cortical neurones and in surviving cranial nerve nuclei and anterior horn cells. Evidence is emerging that some patients with classical MND/amyotrophic lateral sclerosis (ALS), who are thought not to be demented, develop cognitive deficits in the realm of frontal executive functions. Moreover, frontal lobe abnormalities have been demonstrated by neuroimaging. The findings point to a link between FTD/MND and cMND/ALS and suggest that a proportion of patients with cMND/ALS go on to develop FTD. Patients with cMND/ALS may not be equally vulnerable. The hypothesis is that patients who present with bulbar palsy and amyotrophy, rather than corticospinal and corticobulbar features, may be most susceptible to the development of FTD.     

Ubiquitin immunoreactivity in presumed spinal interneurones in motor neurone disease.

Previous studies have demonstrated the presence of ubiquitin-immunoreactivity (Ub-IR) as inclusions and skeins in motor neurones of both the familial and sporadic forms of motor neurone disease (MND). There is evidence that interneurones also degenerate in MND, but Ub-IR in ventral horn spinal interneurones has not been studied previously. Here, Ub-IR was investigated in 1445 presumed interneurones and 1086 presumed motor neurones counted in three random 20-microm sections of the ventral horn of the third lumbar segment of the spinal cord of each of seven controls and seven patients with MND. The ventral horn was divided into four quadrants; the dorsomedial quadrant contains almost exclusively interneurones and the ventrolateral quadrant largely motor neurones. The neurones were also classified by morphological and size criteria into presumed interneurones (< 25 microm) and presumed motor neurones (>or= 25 microm). Ub-IR was classified as inclusions, skeins and dispersed cytoplasmic and nuclear staining. Ub-IR inclusions or skeins were not observed in the controls but 6.6% of neurones (motor neurones and interneurones) showed the presence of dispersed cytoplasm staining and nuclear staining. The incidence of Ub-IR cytoplasmic and nuclear staining was significantly greater in both motor neurones and interneurones of MND patients than controls. Ub-IR was less frequent in MND cases in which a great loss of neurones was observed. Ub-IR was significantly more frequent in motor neurones than interneurones, both in patients and controls. Ub-IR inclusions and skeins were only observed in motor neurones from MND patients. Ub-IR inclusions were not observed in presumed spinal interneurones, while skeins were only seen in three out of 565 of these cells (two of them in the dorsomedial quadrant) in two out of seven patients. Thus, although presumed spinal interneurones occasionally revealed Ub-IR features similar to motor neurones, the rare staining of Ub-IR skeins and the lack of Ub-IR inclusions in interneurones in MND suggests that these neurones only occasionally form ubiquitin-protein conjugates. Neuronal size, rather than type, may be important in determining whether ubiquitin-protein conjugates form in the ventral horn neurones in MND.     

Development of a patient-specific dyspnoea questionnaire in motor neurone disease (MND): the MND dyspnoea rating scale (MDRS)

Motor neurone disease (MND) is a progressive, unremitting and fatal disease. Respiratory dysfunction is common and a significant cause of morbidity. The relationship between subjective dyspnoea and objective measures of lung function have been unexplored in MND. Increasing interest in the specific treatment of respiratory symptoms in MND has highlighted the need for simple, reliable and valid measures to quantify the degree of dyspnoea in this condition. Several generic questionnaires have been developed to rate subjective breathlessness but are inappropriate for use in MND patients as they often assess dyspnoea by exercise-limitation. As yet, there are no published disease-specific measures to assess dyspnoea in MND. In order to accurately and reproducibly measure the subjective experience of dyspnoea in this patient group, we have developed and validated a novel patient-specific dyspnoea questionnaire, the MND dyspnoea rating scale (MDRS). It comprises three domains covering dyspnoea, emotion and mastery and is valid for use in MND patients at all stages of disease progression. In our cohort of 40 unselected patients with MND we have shown that the patients subjective experience of dyspnoea is closely related to emotion and psychological control over the disease. Dyspnoea is not related to objective measures of lung function such as vital capacity, irrespective of limb or bulbar presentation. In conclusion, vital capacity, although useful prognostically, is only one aspect of respiratory function in MND. The MDRS is a reliable and valid tool to rate subjective dyspnoea in MND.     

Motor neurone disease in Lancashire and South Cumbria in North West England and an 8 year experience with enteral nutrition

Motor neurone disease (MND) is a fatal neurodegenerative disease of unknown aetiology. Malnutrition is a common occurrence and an independent risk factor for worse prognosis. However, it remains unclear whether provision of enteral nutrition (EN) through a gastrostomy tube offers any survival advantage. Our aim was to describe the demographic and clinical characteristics of MND in Lancashire and South Cumbria in North West England and the impact of EN on survival in the 8 year period of 2005–2012. Four hundred and seven patients with MND were identified through the Preston MND care and research centre registry giving a crude incidence rate of 3.15/100,000. Three hundred and forty patients with adequate information were included in the final analysis of whom 53.2% were male. The presentation was limb/spinal in 62.1% and bulbar in 37.9% of patients, bulbar onset being more common in elderly females. Mean age of onset was 67.28 years (standard deviation 11.06; range 22.78–93.06). Median survival was 1.98 years (range 1.18–3.05). Ninety-one patients received EN of whom 67% had bulbar onset disease. EN was not associated with a statistically significant survival advantage except for the subgroup who received EN more than 500 days after symptom onset. In conclusion, the early requirement for EN may indicate a prognostically less favourable subgroup.     

运动神经元病患者血浆胰岛素样生长因子-1的变化

目的 探讨运动神经元病（ＭＮＤ）患者血浆胰岛素生长因子－１（ＩＧＦ－１）变化的临床意义。方法 应用放射免疫法测定２１例ＭＮＤ患者血浆ＩＧＦ－１水平,同时测定其血清胰岛素和空腹血糖水平,并设立正常对照组。结果 与正常对照组比较,ＭＮＤ患者血浆ＩＧＦ＿１水平显著下降,虽然两组血糖水平无明显差异,但口才组血浆胰钫 水平明显下降。结论 ＩＧＦ－１系统参与了ＭＮＤ的发病机理,神经营养支持的缺乏是导致髓运动元     

Wilson's disease: normalisation of cortically evoked motor responses with treatment

Summary A newly diagnosed patient with Wilson's disease is reported in whom the only clearly pathological neurophysiological findings before treatment were abnormal electromyographic (EMG) responses evoked by transcranial magnetic brain stimulation. Serial examinations over 10 months following commencement of treatment with D-penicillamine revealed normalisation of EMG responses. Pathophysiologically, the initially abnormal EMG responses probably resulted from reversible impairment of impulse propagation along corticomotoneuronal pathways and/or a reduced excitability of cortical cells due to impaired function of the basal ganglia.     

Population frequencies of neuromuscular diseases—II. Amyotrophic lateral sclerosis (motor neurone disease)

A summary of the world literature on the prevalence of amyotrophic lateral sclerosis (motor neurone disease) has been carried out. Excluding those particular isolates with especially high prevalences (e.g. Guam and the Kii Peninsula of Japan), the mean prevalence among both sexes in other populations is around 41.6 × 10⁻⁶ or 1 in 24,000.     

脑血管病患者经颅磁刺激运动诱发电位的研究

采用经颅磁刺激运动诱发电位（ＭＥＰ）对７２例脑血管病（ＣＶＤ）患者和５０例正常人进行检测。结果：ＣＶＤ患者瘫痪侧上肢磁刺激无反应或皮层潜伏期和中枢传导时间（ＣＭＣＴ）较正常对照组和健侧显著延长（Ｐ＜０．００１）；瘫痪侧下肢磁刺激无反应或ＣＭＣＴ较正常对照组和健侧显著延长（Ｐ＜０．０５）。脑出血与脑梗塞患者ＭＥＰ异常率无显著差异（Ｐ＞０．０５），而与临床病情轻重和病变部位密切相关。提示ＭＥＰ能客观反映ＣＶＤ患者中枢运动传导通路功能受损的情况。     

Cerebral amyloid angiopathy and motor neurone disease presenting with a progressive supranuclear palsy-like syndrome.

We describe a 68-year-old woman who presented with falls, mild limb bradykinesia, axial rigidity, and a severe supranuclear gaze palsy, which failed to benefit from levodopa. She subsequently developed severe apraxia, progressive dysarthria, dysphagia, and a frontal cognitive impairment. Pyramidal weakness with fasciculations and widespread chronic partial denervation appeared shortly before her death from bronchopneumonia, 6 months after disease onset. A severe cerebral amyloid angiopathy diffusely involving the cerebral hemispheres and cerebellum was present at autopsy as well as a second pathological condition indicative of motor neurone disease. Cerebral amyloid angiopathy may rarely present with a progressive supranuclear palsy-like phenotype.     

Motor neurone disease in South Estonia Diagnosis and incidence rate

The current study evaluated the diagnostic standards of MND and epidemiological markers of MND in Estonia. A total of 108 patients were referred to the University Hospital from 1986 to 1995 with the first suggested diagnosis or final diagnosis of amyotrophic syndrome, amyotrophic lateral sclerosis (ALS), progressive bulbar paralysis (PBP) or progressive muscular atrophy (PMA). In addition neurologists of the region and the National Society of Neuromuscular disorders were contacted. Some 94 patients satisfied the diagnostic criteria. The annual incidence rate in South Estonia and in the city of Tartu ranged from 0.5 to 2.8 per 100,000. The mean annual incidence rate in Tartu is 1.98 and in South Estonia in general 1.3. The highest incidence rate was 8.3 for men in the age group 60 to 64 years and 7.49 in the age group 70–74; among female patients the highest incidence rate -4.6 was in the age group from 65 to 69.     

运动神经元病162例的节段性运动神经传导测定分析

目的探讨运动神经元病(motor neuron d isease,MND)常规节段运动神经传导和位移技术检测的特点。方法对162例MND患者和60名健康对照进行常规节段运动神经传导测定,同时对部分神经采用位移技术测定,并进行分析比较。结果(1)健康人常规节段运动神经传导测定显示:近端与远端比较,波幅和面积下降程度均小于20%,时限增宽小于15%;(2)在MND患者,常规节段测定共有76个节段(5.57%)波幅下降超过20%,45个节段(3.30%)面积下降超过20%,76个节段(5.57%)时限延长超过15%。仅有4例(2.5%)患者4条神经的4个常规节段(0.29%)达到运动神经部分性传导阻滞标准,但采用位移技术测定时均未达到短节段传导阻滞的诊断标准。结论在大部分MND患者常规节段运动神经传导测定正常,在部分患者也可以出现“传导阻滞样”的电生理表现,但其发生率极低,进一步采用位移技术测定有助于鉴别。     

运动神经元病患者的记忆功能研究

目的观察运动神经元病(motor neuron disease,MND)患者是否存在记忆功能障碍;并研究患者的病程对其记忆功能的影响。方法对比分析了32例MND患者与60例正常对照的临床记忆量表评分,并比较不同病程的MND患者的记忆功能评分。结果MND患者记忆商、临床记忆量表总等值量表分、指向记忆等值量表分、无意义图形再认等值量表分评分均明显低于对照组(P<0.05),且不同病程的MND患者临床记忆量表各项评分比较无显著性差异(P>0.05)。结论MND患者大多存在记忆障碍,提示MND存在运动区域以外的脑组织受累。MND患者的记忆障碍与病程长短无明显关系。