Cylindrical spirals associated with severe congenital muscle weakness and epileptic encephalopathy

Introduction: Cylindrical spirals are characteristic muscular inclusions consisting of spiraling double‐laminated membranes. They are found in heterogeneous clinical conditions. Methods: We obtained muscle biopsies from 2 young sisters with severe congenital hypotonia, muscle weakness, and epileptic encephalopathy, and identified cylindrical spirals. Results: We found an association between congenital encephalomyopathy and cylindrical spirals. Conclusions: In this morphological and ultrastructural study, we speculate on the origin of these peculiar structures. Muscle Nerve 52 : 895–899, 2015     

Cylindrical spirals in human skeletal muscle.

Muscle biopsies from two patients revealed that numerous type 2 fibers contained large abnormal areas filled with cylindrical spirals. The cytochemical profile of these cylindrical spirals was sufficiently characteristic that they could be distinguished from tubular aggregates. Their electron microscopic appearance was unmistakable. Their origin and significance are uncertain. The diverse nature of the patients' conditions (cramps and malignancy, and an unusual form of spinocerebellar degeneration) indicate that these abnormal structures are not disease specific.     

Muscle pain associated with tubular aggregates and structures resembling cylindrical spirals

A 42-year-old man complained of muscle pain in the legs and episodes of left-sided limb weakness. Light microscopy of his quadriceps muscle showed abundant subsarcolemmal accumulations with typical histochemical features for tubular aggregates. Electron microscopy showed areas filled with tubular aggregates and vesicular profiles. Scattered within some of the tubular aggregates circular profiles reminiscent of cylindrical spirals were seen. The presence of structures resembling cylindrical spirals within tubular aggregates suggest that they may arise from a component of the sarcoplasmic reticulum. There appears to be an intimate relationship between myalgia and these various types of abnormal membranous profiles; however, the pathophysiology remains to be elucidated.     

Cylindrical spirals in skeletal muscle: A further observation with clinical,morphological, and biochemical analysis

Cylindrical spirals are abnormal uniform membranous inclusions in skeletal muscle, usually confined to type 2 fibers. Hitherto, only five cases have been published with various clinical syndromes. Here, a case is presented for the first time with detailed electrophysiological, histometrical, and biochemical analysis: a 60-year-old man with slowly progressing polyneuropathy confirmed by electrophysiological findings, and a history of diabetes, alcoholism, nicotine abuse, and weight reduction. In various muscle biopsies, large aggregates of cylindrical spirals were found almost exclusively in type 2B fibers. Obviously, the aggregates were derived from abnormal perinuclear and, therefore, mainly subsarcolemmal tubulovesicular structures. Morphometrical, histochemical, and biochemical analysis of muscle revealed no further information about the nature of these inclusions. They were not present in skin biopsy containing subcutaneous nerves.     

Evaluating factors that can influence spirography ratings in patients with essential tremor

Spirograph drawings are used in most comprehensive assessments of essential tremor (ET). Nevertheless, several different paradigms are used and no effort has been made to compare these. We used two different cohorts to assess different aspects of spiral rating. In the first, we had subjects simulate different levels of effort by writing (1) 'normally', (2) 'slowly and carefully', (3) 'softly', and (4) 'rapidly' using both their dominant and non-dominant hands. In the second, subjects (1) drew in between the lines of two drawn spirals, (2) traced a previously drawn spirograph, and (3) drew freehand. Subjects drew each with both 'supported' (regular writing) and 'unsupported' writing. The spirals were coded, randomized and blindly rated on a 0-9 scale. Unsupported drawings were consistently rated as worse than supported spirals, and the dominant hand was generally better than the non-dominant hand. Spiral drawn freehand spirals were consistently rated with the lowest scores. Inter-rater and intra-rater reliability were also best for unsupported drawings and tended to be best for 'freehand'. 'Effort' had little effect on ratings. Based on our results, we recommend that assessment of ET include unsupported, freehand spirals.     

Myopathy with tubulin-reactive inclusions in two cats

Many types of inclusions have been described in human myopathies including but not limited to nemaline rod bodies, cylindrical spirals, tubular aggregates, cytoplasmic bodies, reducing bodies, and fingerprint bodies, and hyaline inclusions in myofibrillar myopathy and inclusion body myositis. There are very few reports describing inclusions in spontaneously occurring myopathies in cats, and these reports are limited to nemaline rod myopathy. A myopathy with tubulin-reactive crystalline inclusions has recently been reported in a human patient with a clinical presentation of myalgia and fatigue. Similarly, a myopathy with chronic, slowly progressive muscle weakness has been identified here in two unrelated cats. Inclusions were the only pathological change in skeletal muscle biopsies and, ultrastructurally, groups of crystalline structures were evident that had a subsarcolemmal or central location, rhomboid or rectangular shapes, lacked orientation, and were not membrane bound. The crystalline structures reacted positively with an antibody against tubulin. This feline myopathy may be the equivalent of the human myopathy with tubulin-positive crystalline inclusions.     

High serum creatine kinase levels associated with cylindrical spirals at muscle biopsy

We studied the muscle biopsy from an asymptomatic patient with high serum creatine kinase values. Subsarcolemmal and intermyofibrillar granular inclusions were seen at the light microscopy level. Ultrastructural observation showed clusters of cylindrical spirals (CS). CS are a nonspecific, morphological finding, so far reported only in a few cases, presenting with a wide variety of clinical phenotypes. The case we describe is peculiar because of the complete lack of clinical symptoms. The nature of the CS is unknown; we studied a possible alteration of cytoskeletal proteins using a set of different antibodies against these structures, but none of them reacted with CS. Also, since CS have been described in association with mitochondrial abnormalities, and since in our case CS were strongly positive when stained for succinate dehydrogenase, we performed specific immunohistochemical and genetic studies which ruled out any major mitochondrial alterations.     

The spiral axis as a clinical tool to distinguish essential tremor from dystonia cases

BackgroundTremor is a common feature of a variety of neurological disorders. In genetic studies of essential tremor (ET), investigators need to screen potential enrollees by mail or telephone to exclude those with other neurological conditions, especially dystonia. In clinical settings, the differentiation of ET and dystonia may also be very challenging. We hypothesized that the spiral axis, described below, is a useful screening tool to distinguish ET cases from dystonia cases.MethodsWe analyzed the hand-drawn spirals of 135 individuals enrolled in a genetics study at Columbia University Medical Center. Each of the four spirals was assessed for the presence of a single identifiable tremor orientation axis, and a spiral axis score (range = 0–4) [a single axis on all 4 spirals] was assigned to each enrollee.ResultsThere were 120 ET cases and 15 cases with dystonic tremor. Most (101/120, 84.2%) ET cases had an axis score ≥1 vs. only half (8/15, 53.3%) of the dystonia cases (p = 0.02). Receiver Operator Curve (ROC) analysis revealed that the use of a spiral axis score ≥2 as a cut off would exclude 60.0% of dystonia cases while including 67.5% of ET cases.ConclusionHandwritten spirals appear to have a single predominant axis in more ET than dystonia cases. The evaluation of this axis has moderate diagnostic validity as a screening tool to distinguish ET cases from those with dystonia. Although this study did not assess the utility of this tool in clinical practice settings, future studies should do so.     

一次血管内栓塞治愈基底动脉两侧两个动脉瘤

椎－基底动脉多发性动脉瘤少见，并且治疗困难，其原因是开颅手术容易损伤供应脑干的穿支动脉而导致严重并发症，血管内栓塞术可避免上述问题。作者首次报告一例基底动脉双侧两个动脉瘤，采用自制机械性可脱性微弹簧圈一次血管内栓塞治愈。并对一次血管内栓塞多发性颅内动脉瘤注意事项进行了讨论。     

Evaluation of three different ways of assessing tremor in multiple sclerosis

OBJECTIVES: To examine the comparative reliability and validity of three simple ways of rating upper limb tremor in patients with multiple sclerosis. METHODS: Three examiners independently rated severity of upper limb tremor in patients with multiple sclerosis on a 0-10 scale by studying videotape recordings of patients' examinations, spiral drawings, and handwriting samples. The correlations of the tremor severity scores with scores from arm dexterity tests and a tremor related disability scale were also assessed. RESULTS: Rating tremor on posture had a good intrarater and interrater reliability. However, these reliabilities decreased when kinetic tremor was assessed, in part because dysmetria was a confounding factor. The intrarater reliabilities of rating tremor from spirals and handwriting were also good but the interrater reliabilities were only fair to moderate. Tremor severity scored by all three methods correlated highly with scores obtained from the nine hole peg test, finger tapping test, and a tremor related activities of daily living (ADL) questionnaire, indicating that all three methods were valid ways of assessing tremor in multiple sclerosis. CONCLUSION: Multiple sclerosis tremors in posture can be scored using a clinical rating scale in a valid and reliable way, and from spirals and handwriting samples if the ratings are carried out by the same examiner. However, scoring kinetic tremor was less reliable. In addition, the nine hole peg and finger tapping tests provide useful objective assessments of upper limb function in tremulous patients with multiple sclerosis.     

Validation of digital spiral analysis as outcome parameter for clinical trials in essential tremor

Essential tremor, one of the most prevalent movement disorders, is characterized by kinetic and postural tremor affecting activities of daily living. Spiral drawing is commonly used to visually rate tremor intensity, as part of the routine clinical assessment of tremor and as a tool in clinical trials. We present a strategy to quantify tremor severity from spirals drawn on a digitizing tablet. We validate our method against a well‐established visual spiral rating method and compare both methods on their capacity to capture a therapeutic effect, as defined by the change in clinical essential tremor rating scale after an ethanol challenge. Fifty‐four Archimedes spirals were drawn using a digitizing tablet by nine ethanol‐responsive patients with essential tremor before and at five consecutive time points after the administration of ethanol in a standardized treatment intervention. Quantitative spiral tremor severity was estimated from the velocity tremor peak amplitude after numerical derivation and Fourier transformation of pen‐tip positions. In randomly ordered sets, spirals were scored by seven trained raters, using Bain and Findley's 0 to 10 rating scale. Computerized scores correlated with visual ratings (P < 0.0001). The correlation was significant at each time point before and after ethanol (P < 0.005). Quantitative ratings provided better sensitivity than visual rating to capture the effects of an ethanol challenge (P < 0.05). Using a standardized treatment approach, we were able to demonstrate that spirography time‐series analysis is a valid, reliable method to document tremor intensity and a more sensitive measure for small effects than currently available visual spiral rating methods. © 2011 Movement Disorder Society     

Spiral analysis in Niemann‐Pick disease type C

Spiral analysis is a computerized method of analyzing upper limb motor physiology through the quantification of spiral drawing. The objective of this study was to determine whether spirals drawn by patients with Niemann‐Pick disease type C (NPC) could be distinguished from those of controls, and to physiologically characterize movement abnormalities in NPC. Spiral data consisting of position, pressure, and time were collected from 14 NPC patients and 14 age‐matched controls, and were analyzed by the Mann‐Whitney U test. NPC spirals were characterized by: lower speed (2.67 vs. 9.56 cm/s, P < 0.001) and acceleration (0.10 vs. 2.04 cm/s², P < 0.001), higher loop width variability (0.88 vs. 0.28, P < 0.001), tremor (5/10 vs. 0/10 trials in the dominant hand, P < 0.001), and poor overall spiral rating (2.53 vs. 0.70, P < 0.005). NPC spirals also exhibited sustained drawing pressure profiles that were abnormally invariant with time. Other features, such as the tightness of loop widths, were normal. Our findings reveal that differing aspects of tremor, Parkinsonism, ataxia, and dystonia are quantifiable in NPC patients. © 2009 Movement Disorder Society     

Protein aggregate myopathies

Protein aggregate myopathies (PAM) are an emerging group of muscle diseases characterized by structural abnormalities. Protein aggregate myopathies are marked by the aggregation of intrinsic proteins within muscle fibers and fall into four major groups or conditions: (1) desmin-related myopathies (DRM) that include desminopathies, a-B crystallinopathies, selenoproteinopathies caused by mutations in the, a-B crystallin and selenoprotein N1 genes, (2) hereditary inclusion body myopathies, several of which have been linked to different chromosomal gene loci, but with as yet unidentified protein product, (3) actinopathies marked by mutations in the sarcomeric ACTA1 gene, and (4) myosinopathy marked by a mutation in the MYH-7 gene. While PAM forms 1 and 2 are probably based on impaired extralysosomal protein degradation, resulting in the accumulation of numerous and diverse proteins (in familial types in addition to respective mutant proteins), PAM forms 3 and 4 may represent anabolic or developmental defects because of preservation of sarcomeres outside of the actin and myosin aggregates and dearth or absence of other proteins in these actin or myosin aggregates, respectively. The pathogenetic principles governing protein aggregation within muscle fibers and subsequent structural sarcomeres are still largely unknown in both the putative catabolic and anabolic forms of PAM. Presence of inclusions and their protein composition in other congenital myopathies such as reducing bodies, cylindrical spirals, tubular aggregates and others await clarification. The hitherto described PAMs were first identified by immunohistochemistry of proteins and subsequently by molecular analysis of their genes.     

Spiral analysis-improved clinical utility with center detection

Spiral analysis is a computerized method that measures human motor performance from handwritten Archimedean spirals. It quantifies normal motor activity, and detects early disease as well as dysfunction in patients with movement disorders. The clinical utility of spiral analysis is based on kinematic and dynamic indices derived from the original spiral trace, which must be detected and transformed into mathematical expressions with great precision. Accurately determining the center of the spiral and reducing spurious low frequency noise caused by center selection error is important to the analysis. Handwritten spirals do not all start at the same point, even when marked on paper, and drawing artifacts are not easily filtered without distortion of the spiral data and corruption of the performance indices. In this report, we describe a method for detecting the optimal spiral center and reducing the unwanted drawing artifacts. To demonstrate overall improvement to spiral analysis, we study the impact of the optimal spiral center detection in different frequency domains separately and find that it notably improves the clinical spiral measurement accuracy in low frequency domains.     

Quantification of the drawing of an Archimedes spiral through the analysis of its digitized picture

We have developed a new quantitative analysis of spiral drawing that is able to evaluate any spiral execution and it has not temporal or spatial limitations in the obtaining of specimens. Thirty-one patients with action tremor and 24 control subjects were asked to draw an Archimedes spiral over a print template. Specimens were scanned and then treated through a semiautomatic computer program that reconstructs the temporal sequence of the spiral drawing by the subject. The spirals were first analysed by means of the cross-correlation coefficient with the spiral template. Secondly, the mean and the standard deviation of the distance between each point of the spiral drawing and the corresponding point of the spiral model were determined. Finally, the reconstructed spiral was analysed using the Fourier Transform. Its results were interpreted with the aid of a computer model of a tremulous spiral. The experimental variables were greater in the patients group respect to age-matched controls. There was also a high linear correlation between them and the clinical score given by three neurologists. Finally, Receiver Operating Characteristic (ROC) curves analysis shown that the method classified the spirals better than human ratters.     

Anterior expandable cylindrical cage reconstruction after cervical spinal metastasis resection

Surgical therapy of cervical spine metastases had evolved a in the last years from posterior decompressive approaches to a direct anterior reconstructive approaches. Indication for surgery included intractable neck pain, spinal cord compression and stabilization of impending pathological fractures. We report our experience with expandable cylindrical cages in order to reconstruct and to stabilize cervical spine with metastasis. Between June 2004 and January 2006, a consecutive series of six patients underwent to resection of metastatic tumor in the cervical spine followed by expandable cylindrical cage reconstruction of the anterior vertebral column. All patients achieved immediate stability with neurological preservation. There were no significant complications related to the expandable cages in a mean follow up period of 10.5 months.Expandable cylindrical cages are effective resources for functional reconstruction after tumor resection in patients with cervical metastasis with advantages in the quality of life.     

Zur Ätiologie der Sucht

A psychodramatic explanatory model regarding the origin and upkeep of addiction is prepared in this article, which also includes substance-related addictions and behavioural dependencies. Negative spirals, resulting in the development and manifestation of abusive and addictive behaviour are described with the aid of psychodramatic role-theory and the two forces of the spontaneity-creativity circle (motivational dynamics and self-enhancing feedback).     

Microangiographic studies of denervated,reinnervated and hypertrophic muscles of rats

Summary The behavior of the capillaries of denervated, reinnervated and hypertrophic muscle of rats was investigated with aid of microangiography.The vessels of the denervated muscle ran irregular, formed spirals and their parallel position to the muscle fibers was completely lost. The appearance of vessels after 3 and 6 weeks in the reinnervated muscle was similar to that observed after denervation. The pattern of vessels became more normal 3 months after the operation. The hypertrophic exercised muscles had an irregular course but with less tendency to spiral formation than the atrophic muscles. Their caliber was enlarged. The results showed that in denervated, reinnervated and hypertrophic muscle similar changes in capillary vessels develop. The vessels lose their parallel position to the muscle fibers and have a tendency to spiralization. The changes probably contributed to impairment of the circulation.This work was supported partly by project No. 10.4.2.02. Polish Academy of Sciences and partly by agreement No. 05,002-N with the NIH, Bethesda     

A neural network architecture for figure-ground separation of connected scenic figures

A neural network model, called an FBF network, is proposed for automatic parallel separation of multiple image figures from each other and their backgrounds in noisy gray-scale or multicolored images. The figures can then be processed in parallel by an array of self-organizing Adaptive Resonance Theory (ART) neural networks for automatic target recognition. An FBF network can automatically separate the disconnected but interleaved spirals that Minsky and Papert introduced in their book Perceptrons. The network's design also clarifies why humans cannot rapidly separate interleaved spirals, yet can rapidly detect conjunctions of disparity and color, or of disparity and motion, that distinguish target figures from surrounding distractors. Figure-ground separation is accomplished by iterating operations of a Feature Contour System (FCS) and a Boundary Contour System (BCS) in the order FCS-BCS-FCS, hence the term FBF. The FCS operations include the use of nonlinear shunting networks to compensate for variable illumination and nonlinear diffusion networks to control filling-in. A key new feature of an FBF networks is the use of filling-in for figure-ground separation. The BCS operations include oriented filters joined to competitive and cooperative interactions designed to detect, regularize, and complete boundaries in up to 50% noise, while suppressing the noise. A modified CORT-X filter is described. which uses both on-cells and off-cells to generate a boundary segmentation from a noisy image.