Clinical evolution of pure upper motor neuron disease/dysfunction (PUMMD)

Introduction: PLS is defined as pure upper motor neuron disease/dysfunction (PUMND) beyond 48 months after symptom onset. We know little about its early stages, but such knowledge would help to identify the mechanisms underlying PLS and ALS and determine why PLS patients seem to be protected against lower MND (LMND). Methods: We reviewed 622 MND cases during a 4‐year period and identified 34 patients with PUMND (5.4%). Results: Among 23 cases with follow‐up data/electromyograms (EMGs; 2 had only 1 EMG), 13 (57%) remained classified as PUMND, and 8 (35%) developed LMND (mean, 51.4 months after onset). Of these 8, LMND developed in 3 after 48 months from symptom onset. Patients with PUMND and LMND were more functionally impaired (P = 0.02). Separately, we identified 5 patients with PUMND who developed LMND long after 48 months (range, 50–127 months). Conclusions: PLS belongs to the ALS spectrum, and perhaps all cases eventually develop LMND. Muscle Nerve, 2013     

Dementia with motor neuron disease

Dementia with motor neuron disease has been described as a new clinicopathologic entity and more than 100 cases have been reported in Japan since 1964. The clinicopathologic criteria in the diagnosis of dementia with motor neuron disease are: (i) frontotemporal lobe‐type dementia with insidious onset, mostly in the presenile period; (ii) neurogenic muscular wasting during the course of the illness (amyotrophic lateral sclerosis‐ or SPMA‐like symptoms); (iii) duration from the onset of illness to death of 2–5 years (average, 30.6 months); (iv) both extrapyramidal symptoms and definite sensory deficits are present less commonly; (v) no characteristic abnormalities in the cerebrospinal fluid or electroencephalogram on screening; (vi) no known parental consanguinity or familial occurrence; and (vii) non‐specific, mild to slight degenerative changes in the frontotemporal cortex, hypoglossal nuclei and spinal cord, and frequently in the substantia nigra. Dementia with motor neuron disease is characterized by ubiquitin‐immunoreactive intraneuronal inclusions in cortical layer II and hypocampal dentate granule cells.     

Cognitive impairment in motor neuron disease

A systematic investigation of the cognitive functions of 22 patients affected with motor neuron disease (MND) compared to 36 controls matched for age and education was performed. The MND group showed cognitive performances slightly but significantly lower than the control group; 6 MND patients, however, had decidedly pathological values. Cognitive impairment was stereotyped and global, with sparing of memory. There was no significant difference between patients with isolated involvement of the lower motor neuron and those with associated pyramidal involvement. Our neuropsychological findings are in agreement with previous clinical, neuroradiological and pathological reports indicating extra-motor cerebral involvement in MND.     

Central motor conduction in cerebrovascular disease and motor neuron disease

Conduction in the central motor pathways was studied in 9 patients with cerebrovascular disease (CVD), 13 with amyotrophic lateral sclerosis (ALS) and 3 with spinal progressive muscular atrophy (SPMA). Motor responses evoked in the limb by cortical, cervical and lumbar stimulations were recorded. The central conduction time (CCT) was calculated for each muscle. In patients with CVD, responses to cortical stimulation were unobtainable or delayed in the paretic limb muscles. In patients with ALS the abnormality of central motor conduction had significant correlation with the extensor plantar response. The CCTs were normal in patients with SPMA. This technique demonstrated a subclinical lesion in some patients. We conclude that the new technique of examining motor conduction along the corticospinal tract may be useful to detect a subclinical lesion in the corticospinal tract.     

Cyanide metabolism in motor neuron disease

Cyanide concentrations in whole blood, saliva and urine were measured in 83 patients with motor neuron disease (MND) and age-, sex-matched control subjects consisting of 62 patients with and 49 without neurological disorders. Cyanide levels in whole blood and urine of MND patients were significantly higher than the non-neurological control groups in smokers and non-smokers. Cyanide levels in whole blood of MND patients were also higher than the neurologic control group in smokers, but not in non-smokers. There was no significant difference between the cyanide level and either the clinical types or degree of disability of MND. The results suggest that MND patients possess a disorder in cyanide metabolism.     

Infantile motor neuron disease with autonomic dysfunction and bunina bodies

A 2-month-old girl developed motor neuron disease (MND) with autonomic disturbances and died at the age of 5 months. Neuropathological examination revealed Bunina bodies (BBs) in the lower motor neurons of the lumbar spinal cord. The significance of the presence of BBs and the classification of the MND in this child are discussed. Received: 28 April 1997 / Accepted: 8 July 1997     

Epidemiology of motor neuron disease in northern Sweden

All cases of motor neuron disease (MND), encompassing amyotrophic lateral sclerosis (ALS), progressive bulbar paralysis (PBP) and progressive spinal muscular atrophy (PSMA), in northern Sweden, diagnosed between 1969-1980 have been analysed. 128 cases were found, corresponding to an average annual incidence rate of 1.67 per 100,000. The prevalence on December 31, 1980 was 4.8 per 100,000. Age-specific incidence rates were higher in the high age groups with a maximum at 60-64 years for males, at 70-74 years for females and at 65-69 years for the sexes combined. The median age at onset was 61 years. Clustering was not found in mining districts and overrepresentation of miners and stone treaters was not observed. Minor differences in incidence rates, as measured by the standardized morbidity ratio, SMR, were found between the inland, coastal and mountain areas. The median survival time after onset of disease was 32 months for ALS, 30 months for PBP and 70 months for PSMA. The combined survival rate for all MND cases was 28% after 5 years and 15% after 10 years. The male to female ratio was 1.1:1, and 4.7% were familial cases.     

Chronic multifocal demyelinating neuropathy simulating motor neuron disease

We describe a patient with a chronic acquired predominantly motor polyneuropathy. His clinical picture initially led to a diagnosis of lower motor neuron form of amyotrophic lateral sclerosis. However electrophysiological examination revealed multifocal, prevalently proximal, conduction blocks at sites not prone to compression. Distinguishing this unusual polyneuropathy from motor neuron diseases is critical, since the former is a potentially, treatable disorder.

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Sommario Viene descritto un paziente con polineuropatia cronica acquisita prevalentemente motoria, inizialmente diagnosticata come sclerosi laterale amiotrofica. L'esame elettrofisiologico ha evidenziato blocchi di conduzione prevalentemente prossimali in segmenti nervosi solitamente non soggetti a compressione. Distinguere questa inusuale polineuropatia dalle malattie del motoneurone è di fondamentale importanza sia per quanto riguarda la prognosi che la terapia.

     

Flaviviruses in motor neuron disease

Sporadic motor neuron disease (MND) causes a progressive loss of motor neurons. West Nile virus can attack motor neurons, so we examined whether flavivirus infection could be detected in MND cases. Spinal cord sections from 22 MND cases were stained immunohistochemically with a flavivirus-specific antibody. No staining for flavivirus was seen in any case. Sporadic MND does not appear to arise from a recent infection with a flavivirus.     

The spectrum of lower motor neuron syndromes

Abstract. This review discusses the most important lower motor neuron syndromes. This relatively rare group of syndromes has not been well described clinically. Two subgroups can be distinguished: patients in whom motor neurons (lower motor neuron disease (LMND)) are primarily affected or motor axons and their surrounding myelin (multifocal motor neuropathy (MMN)), both leading to muscle atrophy and weakness.Both hereditary and sporadic forms of LMND have been described. The discussion of recent advances in the genetic knowledge of several hereditary forms of LMND may lead to a better understanding of the pathophysiology and the development of therapeutic strategies. By contrast, the pathogenesis of sporadic LMND is largely unknown. It is, therefore, difficult to consider the various sporadic forms of LMND, discussed in this review, as separate diseases. Because the diagnostic and therapeutic options may differ, it would seem rational to consider sporadic LMND as a spectrum of syndromes which can be distinguished from each other on the basis of clinical presentation.MMN is a lower motor neuron syndrome with presumed immunemediated pathogenesis. Evidence of motor conduction block on nerve conduction studies and a positive response to treatment with intravenous immunoglobulins (IVIg) are considered the most relevant criteria for the diagnosis of MMN. As it is treatable, it is important to distinguish MMN from LMND. Careful electrophysiological analysis in the search for conduction block is, therefore, required in all adult patients with pure lower motor neuron syndromes. For the individual patient, dist inction between the various lower motor neuron syndromes is important as it enables the physician to provide adequate information over the disease course in LMND and to facilitate early treatment in MMN.Supported by a grant from the Prinses Beatrix Fonds.     

Ultra structure of pre-synaptic input to motor neurons in Onuf''s nucleus: controls and motor neuron disease

Ultrastructural analyses of sphincteric motoneurons in Onuf's nucleus at S2 were undertaken in human spinal cord obtained 3-6 h post-mortem from three subjects with no neurological disease ('controls') and five in which death was due to motor neuron disease (MND). Neurons in specified locations within Onuf's nucleus of control subjects ranged between 17.8 and 71.7 microns diameter (mean 38.6 microns). Analyses of synaptology revealed five ultrastructural classes of presynaptic terminal synapsing with the neuronal surface membrane. When classified by size, vesicle morphology, and synaptic site structure these conformed to the S, F, T, M and C-terminals defining somatic motoneurons. No terminals characteristic of autonomic motoneurons were found. In MND subjects, neurons in Onuf's nucleus at S2 were preserved despite a paucity of neurons in medial and lateral motor nuclei and were of similar size range to those in control subjects. The morphological classes of pre-synaptic terminal found in controls, also characterized sphincteric motoneurons in MND subjects, including the C-type terminal. The presence of C-terminals indicates (i) that sphincteric motoneurons are somatic alpha-motoneurons, and (ii) that hypotheses explaining the survival of sphincteric motoneurons in MND on the basis of Onuf's nucleus being an extension of the pre-ganglionic parasympathetic nucleus, or having intrinsic autonomic properties are incorrect.     

New insights in motor neuron disease

In motor neuron disease there is a characteristic pattern of nerve cell loss and degeneration of related pathways. In surviving anterior horn cells several morphologically distinct, but generally non-specific, intracytoplasmic inclusion bodies have been recognized. Recently accumulations of previously unrecognized ubiquitinated material have been described in surviving neurons, which cannot be demonstrated with routine histological methods. These changes appear unique to this disease, and provide a new insight into the underlying pathology that may help understand the pathogenesis of this intriguing disorder. In this article we review the new information on the clinical, toxicological and pathological features of the disease.     

运动神经元病患者胸锁乳突肌肌电图的特征

目的探讨运动神经元病(MND)患者胸锁乳突肌(SCM)肌电图的特征。方法回顾性分析461例MND患者及349例非MND患者的临床和肌电图资料。结果MND组SCM肌电图异常率(60.3%)显著高于非MND组(4.6%)(P<0.01);确诊级MND患者SCM肌电图的异常率(77.4%)明显高于其他诊断级(均P<0.01);MND组中,SCM肌电图的异常率(60.3%)低于上、下肢体肌肉的肌电图(93.2%、84.4%)(均P<0.001);MND患者SCM肌电图异常以自发电位(42.5%)和轻收缩时运动单位电位时限增宽(43.2%)最为常见;MND组有延髓症状者SCM肌电图的异常率(71.7%)明显高于无延髓症状者(54.3%)(P<0.05)。结论MND患者SCM肌电图异常率及其特异性高,为延髓肌受累的指征,有助于MND的诊断与鉴别诊断。     

Motor nerve biopsy studies in motor neuropathy and motor neuron disease

The clinical presentation of motor neuropathy often resembles that of motor neuron disease, sometimes leading to an erroneous diagnosis. Moreover, the underlying pathological process in motor neuropathy has been rarely investigated and there are no systematic studies of the affected motor nerves. We describe a new motor nerve biopsy procedure, performed in 15 patients: 6 with motor neuropathy and 9 with motor neuron disease. The motor branch from the anterior division of the obturator nerve to the gracilis muscle in the thigh was biopsied. In both groups of patients the motor nerves exhibited depletion of myelinated nerve fibers. In motor neuropathy there was a significantly higher density of regenerative clusters of small myelinated fibers in comparison to motor nerves from patients with motor neuron disease. In addition, in 3 patients with motor neuropathy there was evidence for demyelination with thinly myelinated axons and small onion bulb formations. These pathological studies of motor nerve biopsies can help to differentiate motor neuropathy from motor neuron disease. © 1997 John Wiley & Sons, Inc.     

Chorea-acanthocytosis presenting as motor neuron disease

Introduction: Chorea‐acanthocytosis (ChAc) is a rare autosomal recessive disease characterized by involuntary movements, seizures, cognitive changes, myopathy, and axonal neuropathy. Methods: We report a patient who presented with gait impairment and dysarthria. Clinical and neurophysiological assessment disclosed upper and lower motor neuron signs suggestive of motor neuron disease (MND). Results: Later observation of involuntary movements prompted further investigation. Acanthocytes were identified, and the patient's chorein level was low. Genetic studies identified a novel double heterozygous mutation of the chorein gene involving an exon‐stop mutation associated with another mutation that can affect the normal splicing of the RNA. Conclusions: We speculate that this genetic mutation could cause the atypical presentation. ChAc should be included in the differential diagnosis of atypical MND. Muscle Nerve, 2012     

成人起病散发性下运动神经元病基因检测的相关研究

目的探讨成人散发起病的下运动神经元病(lower motor neuron disease,LMND)患者铜锌超氧化物歧化酶1(superoxide dismutase 1,SOD1)基因、运动神经元存活基因(survive motor neuron,SMN)及雄激素受体(androgen receptor,AR)基因对明确诊断疾病类型的作用。方法收集43例成人散发起病表现为LMND的患者取外周血提取基因组DNA,分别进行聚合酶链式反应(PCR)扩增SOD1基因外显子1-5,SMN基因外显子7及男性LMND患者AR基因外显子1,对产物进行高分辨熔解曲线分析、变性聚丙烯酰胺凝胶电泳分析及测序。结果在43例成年LMND患者中,未发现SOD1基因突变。2例男性患者有SMN1外显子7的纯合缺失,诊断为Ⅲ、Ⅳ型脊髓性肌萎缩(SMA)。在31例男性患者中发现3例AR基因外显子1的CAG三核苷酸重复序列数分别为49、50、52,可诊断肯尼迪病。结论对LMND患者进行SMN1基因外显子7及AR基因外显子1检测,可使部分散发或无明确家族史的患者明确诊断,并可对病情及预后进行评估。     

The reorganization of motor units in motor neuron disease

We studied 78 patients with motor neuron disease (MND) using concentric needle electromyography. Analysis on weak and maximal effort was performed using our own, fully automated, computer method, EMG-LAB. In addition to the conventional parameters of single motor unit action potentials (MUAPs) and interference pattern, new criteria were applied: the range of the acting motor units and the functional recruitment order. A total of 375 muscles of MND patients and 120 control muscles were investigated. The electromyographic data were analyzed separately in five groups of muscles, classified A, B, C, D, and E according to their clinical condition. Those results allowed us to discern six neurophysiological stages (N _{0, 1, 2, 3, 4, 5}) from the early to the most advanced phase. It has been confirmed that reinnervation in MND is adequate to compensate for the loss of over 50% of motor neurons but it is only a transitory phase in the morbid course. At stages N_0–5, the electrophysiological data reflect structural and functional integrity of the functioning motor units. Evaluation of not only single MUAPs but also of the full range of acting motor units and their recruitment order allowed a deeper look into the underlying pathophysiological mechanisms. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 306–315, 1997.