Macroelectromyography in progressive post-polio muscular atrophy

A prospective 2-year clinical and macro-EMG follow up was completed in 30 post-polio survivors (19 women and 11 men, aged from 46 to 62 years). The median macro-MUPs amplitudes from either biceps brachii or tibial anterior muscles were estimated. A decrease in muscle strength > 1 MRC grade in the tested extremity was found in five patients (fulfilling criteria for progressive post-polio muscle atrophy-PPMA), and 17 post-polio patients complained of new weakness (Including five PPMA subjects). In seven healthy volunteers the changes in the median macro-MUPs amplitudes on serial examination varied from ?18.8 to +22.4%. In 13 clinically stable patients the change in macro-MUPs amplitude over 2 years did not exceed 25% of the initial value, in comparison with nine of 17 patients with new complaints displaying a > 25% change in the macro-MUPs amplitude, with predominant decrease (6 of 9). All five PPMA patients showed a >25% change in the macro-MUPs amplitude with predominant decrease (+ 33, ?27, ?42, ?50 and ?60%). There was a statistically significant difference in the change of the median macro-MUPs amplitudes between PPMA group (n ? 5) and post-polio patients without objective decline in muscle strength (n = 25; p < 0.05; the Mann–Whitney U test). These findings support the hypothesis of the distal degeneration of abnormally enlarged motor units as a cause of PPMA and show the usefulness of serial measurement in the assessment of PPMA.     

Ultrasound evaluation of fetal movements in pregnancies at risk for severe spinal muscular atrophy

We studied spinal muscular atrophy (SMA) during human development to identify possible delays or alterations in fetal movements detectable by ultrasound. We evaluated 29 pregnancies at risk for severe SMA performing 2D-ultrasound around 11-14 weeks, prior to prenatal molecular testing of the SMN1 gene. We charted the occurrence of generalized body movements, isolated movements of arms and legs, head movements, startle and hiccup. Fetuses were diagnosed as healthy (n = 12), carriers (n = 10) or affected (n = 7) according to the SMN1 molecular testing results obtained. SMN2 copies were also tested in the seven affected fetuses, six of whom showed two SMN2 copies and one a unique SMN2 copy. The movements under study were observed in all recordings, regardless of group and the SMN2 copies. At the gestational age examined, we did not observe a qualitative early limitation of movements in fetuses with SMA, even in cases predicted to develop a severe neonatal form.     

Mirror movements in patients with Parkinson's disease

Mirror movements (MM) refer to ipsilateral involuntary movements that appear during voluntary activity in contralateral homologous body regions. This study aimed to compare the frequency and distribution of MM in an unselected sample of 274 patients with Parkinson's disease (PD) and 100 healthy subjects, and to check a possible relationship between MM and parkinsonian features. MM of the hand were scored according to the Woods and Teuber scale. The frequency of MM was lower in PD patients than in healthy subjects (29% vs. 71%, P < 0.0001). The distribution of MM also differed in the two groups being often bilateral in healthy subjects, invariably unilateral in PD patients. When parkinsonian signs were unilateral, MM always manifested on the unaffected side; when parkinsonian signs were bilateral, MM manifested on the less affected side. PD patients manifesting MM scored significantly lower on Hohen and Yahr staging than patients without MM. Likewise, there was a significant inverse correlation between the intensity of MM as rated by the Woods and Teuber score and HY staging (r = ?0.16, P < 0.01). The low frequency of MM in PD probably relates to the complex interactions between the pathophysiological mechanisms leading to parkinsonian signs and the mechanisms responsible for movement lateralization. © 2007 Movement Disorder Society     

Nemaline bodies in spinal progressive muscular atrophy

Summary Numerous nemaline bodies were demonstrated in the pectoralis major muscle of an autopsy case of a 52-year-old woman, who died of respiratory failure after having suffered from spinal progressive muscular atrophy for 1 year. Rod-like structures ultrastructurally indistinguishable from classical nemaline bodies were abundant in both normal-appearing and atrophic myofibers of the pectoralis major muscle but not in the appendicular skeletal muscles. Morphometric analysis of spinal anterior horn cells clearly showed severe depopulation of somatic motor neurons in the lower cervical cord segments. The present case may provide further support for the neurogenic nature of nemaline body formation.     

Cortical atrophy differentiates Richardson's syndrome from the parkinsonian form of progressive supranuclear palsy

To determine whether brain atrophy differs between the two subtypes of progressive supranuclear palsy (PSP), Richardson's syndrome (PSP‐RS), and PSP parkinsonism (PSP‐P), and whether such atrophy directly relates to clinical deficits and the severity of tau deposition. We compared 24 pathologically confirmed PSP cases (17 PSP‐RS and 7 PSP‐P) with 22 controls from a Sydney brain donor program. Volume loss was analyzed in 29 anatomically discrete brain regions using a validated point‐counting technique, and tau–immunoreactive neurons, astrocytes and oligodendrocytes/threads semiquantified. Correlations between the two pathological measures and the presence or absence of cardinal PSP symptoms were investigated. Cortical atrophy was more severe in PSP‐RS than PSP‐P and affected more frontal lobe regions (frontal pole, inferior frontal gyrus). The supramarginal gyrus was atrophic in both subtypes. Additionally, atrophy of the internal globus pallidus, amygdala, and thalamus was more severe in PSP‐RS. As expected, more severe frontal lobe tau pathology differentiated PSP‐RS from PSP‐P. No correlations were found between the degree of atrophy and severity of tau pathology in any region assessed, or between the severity of atrophy or tau pathology and the presence or absence of cardinal PSP symptoms. Our study shows that thalamocortical atrophy is a defining feature of PSP‐RS, but this atrophy does not correlate with the presence of any specific cardinal clinical feature. Interestingly, there is a disassociation between tau pathology and atrophy in the brain regions affected in PSP‐RS that requires further investigation. © 2010 Movement Disorder Society     

Amantadine effectiveness in multiple system atrophy and progressive supranuclear palsy

Progressive Supranuclear palsy (PSP) and multiple system atrophy (MSA) each respond poorly to most anti-parkinsonian drugs. We assessed PSP and MSA cases seen between 1970 and 1996 for response to amantadine (Amd) 100 mg twice daily. Of 13 MSA cases (six females, seven males), eight (61.5%) improved, four (30.8%) did not benefit and one had insufficient documentation. Adverse effects were observed in three (23.1%) cases. Of 14 PSP (three females, 11 males), six (42.9%) had some improvement, five (35.7%) had no benefit, and three (21.4%) had inadequate documentation. Adverse effects were noted in three (28.6%) cases. Improvement is likely related to NMDA antagonist properties of Amd. We recommend consideration of Amd in the management of both PSP and MSA.     

Spectral signatures of mirror movements in the sensori‐motor connectivity in kallmann syndrome

Mirror movements (MM) might be observed in congenital and acquired neurodegenerative conditions but their anatomic‐functional underpinnings are still largely elusive. This study investigated the spectral changes of resting‐state functional connectivity in Kallmann Syndrome (hypogonadotropic hypogonadism with hypo/anosmia with or without congenital MM) searching for insights into the phenomenon of MM. Forty‐four Kallmann syndrome patients (21 with MM) and 24 healthy control subjects underwent task (finger tapping) and resting‐state functional MRI. The spatial pattern of task‐related activations was used to mask regions and select putative motor networks in a spatially independent component analysis of resting‐state signals. For each resting‐state independent component time‐course power spectrum, we extracted the relative contribution of four separate bands: slow‐5 (0.01–0.027 Hz), slow‐4 (0.027–0.073 Hz), slow‐3 (0.073–0.198 Hz), slow‐2 (0.198–0.25 Hz), and analyzed the variance between groups. For the sensorimotor network, the analysis revealed a significant group by frequency interaction (P = 0.002) pointing to a frequency shift in the spectral content among subgroups with lower slow‐5 band and higher slow‐3 band contribution in Kallmann patients with MM versus controls (P = 0.028) and with lower slow‐5 band contribution between patients with and without MM (P = 0.057). In specific regions, as obtained from hand motor activation task analysis, spectral analyses demonstrated a lower slow‐5 band contribution in Kallmann patients with MM versus both controls and patients without MM (P < 0.05). In Kallmann syndrome, the peculiar phenomenon of bimanual synkinesis is associated at rest with regionally and spectrally selective functional connectivity changes pointing to a distinctive cortical and subcortical functional reorganization. Hum Brain Mapp 39:42–53, 2018. © 2017 Wiley Periodicals, Inc.     

进行性脊肌萎缩症129例临床分析

目的探讨进行性脊肌萎缩症(PSMA)的临床特点、诊断与鉴别诊断。方法回顾性分析129例PSMA患者的临床资料。结果本组患者均隐袭起病,逐渐加重,男性多见,发病年龄65.9%患者>50岁。首发症状以单侧上肢无力和肌萎缩为多见(65.9%),均表现为下运动神经元损害的症状和体征,51.9%患者出现延髓麻痹症状;肌电图检查均提示神经源性损害;易误诊为颈或腰椎病。结论本病是一组慢性进行性下运动神经元疾病,病变可累及延髓。诊断主要依据临床表现和肌电图。     

Spinal muscular atrophy associated with progressive myoclonus epilepsy

A rare syndrome characterized by lower motor neuron disease associated with progressive myoclonic epilepsy, referred to as “spinal muscular atrophy associated with progressive myoclonic epilepsy” (SMA‐PME), has been described in childhood and is inherited as an autosomal recessive trait. SMA‐PME is caused by mutation in the ASAH1 gene encoding acid ceramidase. Ceramide and the metabolites participate in various cellular events as lipid mediators. The catabolism of ceramide in mammals occurs in lysosomes through the activity of ceramidase. Three different ceramidases (acid, neutral and alkaline) have been identified and appear to play distinct roles in sphingolipid metabolism. The enzymatic activity of acid ceramidase is deficient in two rare inherited disorders; Farber disease and SMA‐PME. Farber disease is a very rare and severe autosomal recessive condition with a distinct clinical phenotype. The marked difference in disease manifestations may explain why Farber and SMA‐PME diseases were not previously suspected to be allelic conditions. The precise molecular mechanism underlying the phenotypic differences remains to be clarified. Recently, a condition with mutation in CERS1, the gene encoding ceramide synthase 1, has been identified as a novel form of PME. This finding underlies the essential role of enzymes regulating either the synthesis (CERS1) or degradation (ASAH1) of ceramide, and the link between defects in ceramide metabolism and PME.     

Late onset ataxia phenotype in dentatorubro-pallidoluysian atrophy (DRPLA)

We clinically and genetically studied three patients in a family with dentatorubro-pallidoluysian atrophy (DRPLA). The proband patient had 58/24 CAG repeat alleles of the DRPLA gene (normal ≤ 34 repeats). Cerebellar ataxia first developed in the 6–7^th decades and was the predominant feature for more than 10 years in all three, after which two of them manifested dementia and choreiform movements in the advanced stage. Atrophy of the cerebellum and brain stem an CT or MRI had suggested dominant spinocerebellar ataxia as a diagnosis in their ataxia-predominant stage, with a diagnosis of DRPLA being impossible based on the clinical findings alone. Our experience implies that DRPLA must be taken into account in the differential diagnosis of late onset ataxic disorders, since it can easily be overlooked. Received: 2 April 2001, Received in revised form: 23 July 2001, Accepted: 21 August 2001     

Therapeutic considerations in cerebellopontine angle lipomas inducing hemifacial spasm

Lipoma is a very rare tumour at the cerebellopontine angle. We report a case of incomplete hemifacial spasm, associated with a lipoma involving and compressing both facial and acoustic nerves at their origin in the brainstem. The patient was treated with medical therapy (botulinum toxin A) and surgery. We present a review of the last ten years of the literature, with particular regard to management. Received: 20 January 2000 / Accepted in revised form: 24 November 2000     

Quantitative evaluation of mirror movements in adults with focal brain lesions

Mirror movements (MM), involuntary movements of homologous muscles opposite to unilateral limb activity, decrease in the course of motor development, but may reappear in adults after brain damage. To better characterize this type of acquired MM, grip forces of 36 healthy subjects and 35 patients suffering from focal brain lesions were compared. Holding force transducers in a pinch grip between thumb and index fingers of each hand, subjects had to repeatedly change the grip force in one hand, whilst the other (mirror) hand just had to prevent the manipulandum from dropping. In a second task, force changes had to be produced either in a symmetric or in an antiparallel manner. No significant group differences between patients and controls in the extent of coupling were found. During unimanual squeezing, only six patients had a co-activation in the pathologic range. Whilst performing bimanual asymmetric grip force changes, pathologic coupling was seen only in five patients. No association was found between the presence of pathologic MM and clinical or neuroanatomical features. Brain lesions in adults seem only rarely to be associated with pathologic MM. They might be non-specific and not related to the characteristics of the lesion.     

Dynamic aspects of peripheral nerve changes in progressive neural muscular atrophy

Summary Serial nerve biopsies were performed at an early, and at an advanced stage of the disease in 2 patients with progressive neural muscular atrophy. The early biopsy showed a complete loss of the large diameter and thickly myelinated fibres, as well as an expansion of the endoneurial interstitium in both cases. Myelinated and unmyelinated fibres exhibited axonal degeneration in all biopsies occasionally. Onion bulb formation, a typical feature of peripheral neuropathy in neural muscular atrophy, was found to be prominent only in the latter biopsies. As regards the formal pathogenesis of hypertrophic neuropathy in neural muscular atrophy, axonal dystrophy and interstitial changes of the endoneurium were regarded as primary phenomena, demyelination and onion bulb formation as secondary. A possible causal relation between axonal dystrophy and interstitial changes, observed in these cases, is discussed in the light of the present literature.

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Zusammenfassung Bei 2 Patienten mit progressiver neuraler Muskelatrophie wurden Nervenbiopsien jeweils in einem frühen und in einem fortgeschrittenerem Stadium der Erkrankung entnommen und verglichen. In beiden Fällen zeigten bereits die frühen Biopsien ein völliges Fehlen der großkalibrigen, dickbemarkten Axone. Ebenfalls als frühe Veränderung wurde eine Erweiterung des endoneuralen Interstitiums festgestellt. Eine geringe Anzahl der vorhandenen bemarkten und unbemarkten Axone in allen Biopsien wies degenerative Veränderungen auf. Die für die progressive neurale Muskelatrophie typische Zwiebelschalenbildung der Schwannschen Zellen — möglicherweise eine Reaktion auf wiederholte De-und Remyelinisierungsvorgänge um dystrophische Axone — trat erst in den späteren Biopsien deutlicher hervor. Hinsichtlich der formalen Genese der hypertrophischen Neuropathie bei neuraler Muskelatrophie sind nach diesen Beobachtungen axonale Dystrophie und interstitielle Veränderungen des Endoneuriums als primäre Entmarkung und Zwiebelschalenbildung als sekundäre Phänomene zu betrachten. Die Möglichkeit einer kausalen Beziehung zwischen axonaler Dystrophie und interstitiellen Veränderungen wird an Hand der vorliegenden Befunde und Literatur diskutiert.

     

Klinefelter's syndrome associated with progressive muscular atrophy simulating Kennedy's disease

Kennedy''s disease, an X-linked spinal and bulbar muscular atrophy, is characterized by loss of lower motor neurons. Mild sensory deficits, gynecomastia and infertility may be observed. Klinefelter''s syndrome is a variation of sex chromosome disorder characterized by hypogonadism, gynecomastia and azoospermia, and the most frequent karyotype is XXY. A 55-year-old man who presented with slowly progressive and diffuse neurogenic muscle atrophy without bulbar or sensory symptoms. He also had Klinefelter''s syndrome. Genetic study of Kennedy''s disease was normal. Our patient differs from those with Kennedy''s disease in the absence of bulbar and sensory symptoms. It is suggested that the X chromosome plays an important role in the biology of motor neurons.     

Severe degenerative cortical and cerebellar atrophy and progressive dementia in a young adult

Abstract

A 32-year-old patient is described who presented with severe cognitive deficits and major cortical and cerebellar atrophy. Investigations included numerous clinical laboratory tests, magnetic resonance imaging, [¹⁸F]2-fluoro-2-deoxy-D-glucose positron emission tomography and detailed neuropsychological examinations. Tests covered mood, intelligence, attention and concentration, language, verbal fluency, various memory abilities, and cognitive flexibility. Furthermore, some experimental testing procedures were applied, such as drawing objects, and transcoding verbal and Arabic numerals. Laboratory findings failed to give any indication for viral, bacterial, genetic or metabolic diseases, or for chronic intoxication. In particular, no presenilin genes were found. Neuroradiology revealed very severe cortical and less severe cerebellar degeneration. In most neuropsychological tests, the patient was greatly impaired. In spite of some inconsistencies at the anatomical and cognitive levels, it is concluded that, in spite of his young age, the patient suffered from an unusual from of Alzheimer's disease.     

A survival analysis of 155 cases of progressive muscular atrophy

We performed a survival analysis of 155 cases of progressive muscular atrophy (PMA). In about half the cases, hands were involved first, the lower limbs in 30% and the shoulder girdle in 23%. The lifetables of PMA, adjusted to the expected mortality, showed a survival rate of 61.3% and 56.4% at three and five years, respectively. The location of onset symptoms did not modify the life expectancy, whereas the age of the patients at the moment of first diagnosis had a great influence on the course of the disease. The patients were further subdivided in two groups on the basis of the diffusion of the neuromuscular damage at the moment of the diagnosis. The course of the patients with a localized disease was markedly better than that of subjects with widespread disease. Some hypotheses are made about the latter group of cases.     

A patient with simplified gyral pattern followed by progressive brain atrophy

We present the case of a three-year-old boy who suffered from intractable epilepsy from birth, and who displayed microcephaly and severe developmental delay. Neuroradiological examination revealed the presence of simplified gyri of the cerebral cortex, and increased signal intensity changes in the cerebral white matter on T2-weighted magnetic resonance imaging. A tentative diagnosis of congenital cortical malformation was made, but unexpectedly, the cerebrum, cerebellum, and pons showed a progressive atrophy during the follow-up period. The basal ganglia and thalamus were relatively spared. Investigations could find no evidence of leukodystrophies, metabolic disorders, hereditary brain anomalies, or congenital central nervous infections. This case may represent a novel type of neurodegenerative disease with malformation of cortical development.