Disease-specific patterns of neuronal loss in the spinal ventral horn in amyotrophic lateral sclerosis, multiple system atrophy and X-linked recessive bulbospinal neuronopathy, with special reference to the loss of small neurons in the intermediate zone

Terao, S; Sobue, Gen; Hashizume, Yoshio; Mitsuma, Terunori; Takahashi, Akira

doi:10.1007/bf00863768

Cited by 58 publications

(50 citation statements)

References 44 publications

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“…26 The pathology of this condition is that of ALS, with extensive myelinated fiber loss in the lateral corticospinal tracts of the thoracic and lumbar spinal cord segments. 27,28 We have shown in this study that the natural history of the FA and FL syndromes differs from more typical forms of ALS. The FA and FL syndromes have a significantly better prognosis in terms of median and 5-year survival rates compared to bulbar and limb onset ALS.…”

Section: Resultsmentioning

confidence: 60%

Natural history and clinical features of the flail arm and flail leg ALS variants

Wijesekera¹,

Mathers²,

Talman³

et al. 2009

Neurology

226

201

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Objective: We sought to define the significance of brachial amyotrophic diplegia (flail arm syndrome [FA]) and the pseudopolyneuritic variant (flail leg syndrome [FL]) of amyotrophic lateral sclerosis (ALS; motor neuron disease). Methods:We analyzed survival in clinic cohorts in London, UK (1,188 cases), and Melbourne, Australia (432 cases). Survival from disease onset was analyzed using the Kaplan-Meier method and Cox proportional hazards model. Results:In the London cohort, the FA syndrome represented 11% and the FL syndrome 6% of the sample. Median survival was 35 months for limb onset and 27 months for bulbar onset ALS, whereas this was 61 months for FA syndrome (p Ͻ 0.001) and 69 months for FL syndrome (p Ͻ 0.001). Five-year survival in this cohort was 8.8% for bulbar onset, 20% for limb onset, 52% for FA syndrome, and 64% for FL syndrome. The ratio of men to women was 4:1 in the FA group compared to 2:1 in other limb onset cases. Excluding lower motor neuron FA and FL cases, progressive muscular atrophy comprised 4% of the sample and had a prognosis similar to typical limb onset ALS. In the Melbourne cohort, median survival for limb onset ALS was 31 months, bulbar onset 27 months, FA syndrome 66 months (p Ͻ 0.001), and FL syndrome 71 months (p ϭ 0.001). Amyotrophic lateral sclerosis (ALS) comprises several clinical phenotypes united by a common cellular and molecular pathology. Conclusions:1 The three main clinical categories defined by Aran, Charcot, Duchenne, and others in the 19th century and which were subsequently shown to have both diagnostic and prognostic significance were progressive bulbar palsy (bulbar onset ALS), classic limb onset (Charcot) ALS, and a lower motor neuron form termed progressive muscular atrophy (PMA).2-5 Prognostic factors in these forms of ALS have been delineated through clinic and population-based studies. 6,7 Bulbar onset tends to have a worse prognosis than limb onset, and both forms have a worse prognosis than PMA.2,4-7 However, these three phenotypic categories do not fully capture the spectrum of clinical heterogeneity in ALS. This heterogeneity may contribute to diagnostic error and delay, and with the advent of large-scale whole genome studies that have the potential to identify genetic variants influencing both risk and phenotype,

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Section: Resultsmentioning

confidence: 60%

Natural history and clinical features of the flail arm and flail leg ALS variants

Wijesekera¹,

Mathers²,

Talman³

et al. 2009

Neurology

226

201

View full text Add to dashboard Cite

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“…However, cases with pyramidal signs and absence of spinal cord pyramidal tract degeneration have been described (30,40). This clinicopathological dissociation may be accounted for by involvement of small neurons in the ventral spinal horn, which has been linked to spasticity and hyperreflexia in MSA (129). Although plantar extensor responses and hyperreflexia were common in this literature series, pyramidal weakness and spastic gait were rare, especially as presenting feature.…”

Section: Cerebellar Ataxia and Pyramidal Signsmentioning

confidence: 96%

“…Although moderate or severe degenerative change of the anterior horn cells was noted in 32% of 106 cases, subregional vulnerability was reported in only one study of six MSA cases. These authors found a marked reduction in small anterior horn neurons in the intermediate zone, whereas large and medium-sized neurons of the medial and lateral nuclei tended to be preserved (129).…”

Section: Pathological Featuresmentioning

confidence: 97%

Multiple system atrophy: A review of 203 pathologically proven cases

Tison²,

et al. 1997

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We report the clinicopathological features of 203 cases of pathologically proven multiple system atrophy (MSA) from 108 publications up to February 1995. The majority of patients showed symptoms in their early fifties, and men were more commonly affected than women (ratio of 1.3:1). Most patients suffered from some degree of autonomic failure (74%). Parkinsonism was the most common motor disorder (87%), followed by cerebellar ataxia (54%) and pyramidal signs (49%). The response to levodopa was poor in most patients, but there was a subgroup with a good response, who also often developed axial levodopa-induced dyskinesias. Other characteristic features included severe dysarthria, stridor, and, in a few patients, contractures and dystonia (antecollis). Mild or moderate intellectual impairment occurred in some cases, but severe dementing illness was most unusual. The main pathological change comprised cell loss and gliosis in the putamen, caudate nucleus, external pallidum, substantia nigra, locus ceruleus, inferior olives, pontine nuclei, cerebellar Purkinje cells, and intermediolateral cell columns of the spinal cord. However, other neuronal populations were also involved to varying degrees, such as the thalamus, vestibular nucleus, dorsal vagal nucleus, corticospinal tracts, and anterior horn cells. Characteristic glial and/or neuronal cytoplasmic inclusions were identified in all cases in which they were sought, irrespective of clinical presentation. Akinesia correlated with the degree of nigral and putaminal cell loss, whereas rigidity was related only to the later. Tremor was unrelated to cell loss at any site. Ataxia correlated with the degree of olivopontocerebellar atrophy. Pyramidal signs were associated with pyramidal tract pallor. Our analysis also confirmed an association of postural hypotension with intermediolateral cell column degeneration.

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“…The neuropathological basis of the nerve conduction abnormalities is most probably loss of large neurons in the ventral horn and reduction of myelinated sural nerve fibers [9, 10, 11, 12, 13]. The latter might be due to degeneration of dorsal root ganglion neurons.…”

Section: Discussionmentioning

confidence: 99%

Nerve Conduction Studies in Multiple System Atrophy

et al. 2000

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To study the frequency and severity of peripheral neuropathy in multiple system atrophy (MSA), we performed nerve conduction studies in 42 MSA patients suffering from either cerebellar MSA (MSA-C) or parkinsonian MSA (MSA-P). Abnormal nerve conduction was present in 24% of the patients. Abnormalities were significantly more frequent in MSA-P (43%) compared to MSA-C (14%). Motor nerve conduction velocities were reduced in 4% of the MSA-C and in 7% of the MSA-P patients. Abnormal compound muscle action potentials were more frequent in MSA-P (29% versus 7% in MSA-C) pointing to a more pronounced loss of motor axons in this subgroup. Sensory nerve conduction velocities were abnormal in 4% of the MSA-C and 14% of the MSA-P patients, and mean sensory nerve action potentials were normal in all MSA-C and reduced in 7% of the MSA-P patients. The data provide evidence that the peripheral nervous system is differentially affected in MSA-C and MSA-P.

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Disease-specific patterns of neuronal loss in the spinal ventral horn in amyotrophic lateral sclerosis, multiple system atrophy and X-linked recessive bulbospinal neuronopathy, with special reference to the loss of small neurons in the intermediate zone

Cited by 58 publications

References 44 publications

Natural history and clinical features of the flail arm and flail leg ALS variants

Natural history and clinical features of the flail arm and flail leg ALS variants

Multiple system atrophy: A review of 203 pathologically proven cases

Nerve Conduction Studies in Multiple System Atrophy

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