Rembrandt's 'Beggar with a wooden leg' and other comparable prints.

Rembrandt's etching of a beggar with a wooden leg is notable because the two lower limbs of the presumed beggar are present and not deformed. Using the facilities of four specialised Dutch art institutes, we carried out a systematic investigation to find other etchings and engravings of subjects with artificial legs supporting non-amputated limbs, from the period 1500 to 1700 AD. We discovered 28 prints produced by at least 18 artists. Several offered clues to a disorder of a knee, the lower leg or the foot. All individuals were adult males, suggesting the probability of traumatic lesions. We conclude that in this period artificial legs were not only used in the case of absence of part of a lower limb, but also for other reasons, notably disorders of the knee, lower leg or foot. They may also have been used to attract compassion.

Vinken and Bruyn's Handbook of Clinical Neurology. A witness of late-twentieth century neurological progress.

Vinken and Bruyn's Handbook of Clinical Neurology (HCN) is best characterized as an encyclopedia. In this paper we describe the origin, production, and reception of HCN. Data were gathered from a literature search, by screening of HCN-volumes, interviewing key-role persons and a study of an HCN-archive. The initiative for HCN was taken by two Excerpta Medica staff members, the one a strategist with expertise in information systems, the other a gifted neurologist with an expert knowledge of who is who in the world of neurological literature. Within a period of 38 years, 2799 authors, 28 volume editors, the two initiators, and a third chief editor for the American continent described the whole of neurology in 1909 chapters on all together 46,025 pages (excluding index volumes). HCN was sold mainly to medical institutes in affluent countries. A digital version of the revised edition was proposed by the editors but refused by the publisher for commercial reasons. HCN was in general well received by book reviewers. The main criticisms concerned the price of the volumes, lack of editorial control, inadequacy of indexes, and lack of cross references. HCN offers unrivalled information on the state of the art of the clinical neurosciences in the second half of the twentieth century. In addition, it contains extensive reviews of the history of neurological diseases in the volumes of the original edition.

[The practice guideline 'Dermatomyositis, polymyositis and sporadic inclusion body myositis']. / Richtlijn 'dermatomyositis, polymyositis en sporadische "inclusion body"-myositis'.

This guideline presents recommendations for the diagnosis and treatment of dermatomyositis, polymyositis and sporadic inclusion body myositis (sIBM) according to the best available evidence. Characteristic skin abnormalities can be sufficient for the diagnosis of dermatomyositis. In case of doubt, a skin biopsy is advisable. A muscle biopsy is indicated when other examinations are inconclusive and the musculature is involved. The working group considers screening for cancer to be required in adults with dermatomyositis and presents recommendations for the way that this should be done. At least one-third of all patients with polymyositis has, or will develop, an associated inflammatory connective tissue disease. If a patient with a connective tissue disease develops symmetrical, proximal muscle weakness in the course of weeks or months, this may be assumed to be due to polymyositis. In the absence ofpre-existing connective tissue disease, demonstration of a mononuclear cell infiltrate in muscle tissue is a prerequisite for the diagnosis ofpolymyositis. The histopathology of muscle tissue is used as the gold standard for the diagnosis of sIBM. The practice guideline presents criteria for the concept 'activity' of myositis. Disease activity serves as a guideline for the treatment of polymyositis and dermatomyositis. The treatment of choice for dermatomyositis and polymyositis is high-dose prednisone. Physical activity does not have a negative effect on the course of these diseases. The long-term prognosis ofdermatomyositis and polymyositis is not well known. The clinical course of sIBM is slowly progressive.

[The symptomatic treatment of amyotrophic lateral sclerosis]. / De symptomatische behandeling van amyotrofische laterale sclerose.

Patients with amyotrophic lateral sclerosis (ALS) have symptoms of progressive muscle weakness, of disturbed speech and swallowing, and in the terminal phase those of respiratory weakness. Treatment options, in particular those for excessive weight loss and respiratory weakness, should be introduced to the patients and their families when the patient is emotionally capable and before dysarthria severely hampers communication. Special equipment for keeping the patient as mobile as possible should be made available much earlier than in the case of other diseases of the muscles as in ALS progression is much faster. Cramps, pathological crying or laughter, spasms, and spasticity can all be treated by medication. When speech can no longer be understood, adaptive strategies such as sign language, mime, posture and communication apparatus varying from a note pad to advanced computer systems can be used. Sialorrhoea, caused by difficulty swallowing with its accompanying danger of aspiration can be halted by the use of medication, by radiotherapy and by the injection into the salivary glands of botulin A toxin. Weight loss, also a result of dysphagia, can be avoided by eating frequent small meals or if necessary performing a percutaneous endoscopic or radiological gastroscopy. Excess mucus in the respiratory tract can be treated with anticholinergics. Difficulty in coughing up thick and sticky mucus cannot always be adequately helped. Respiratory weakness is treatable by external respiratory supportive therapy using a nasal mask, as well as invasive respiratory support via a trachcostoma and by treating the symptoms of respiratory weakness. The latter form of treatment is palliative and forms part of terminal care. During the terminal phase restlessness, anxiety, pain, and dyspnoea require the most attention. Treatment requires careful multidisciplinary cooperation.

[Amyotrophic lateral sclerosis: mechanical ventilation--or not right?]. / Amyotrofische laterale sclerose: beademen--of juist niet?

In two patients (men aged 64 and 62 years, respectively) with amyotrophic lateral sclerosis (ALS) tracheostomy ventilation was initiated following (imminent) acute respiratory failure; in one patient this was done because advance directives were lacking, while in the other non-invasive ventilation (NIPPV) was no longer an option. A third ALS patient, a woman aged 36 years, already had chronic respiratory failure when she presented at the local centre for home mechanical ventilation. As a result, the placement of a percutaneous endoscopic gastrostomy (PEG) was impossible. Instead, she had to use a nasopharyngeal feeding tube, which diminished the effectiveness of her NIPPV. The fourth patient, a man aged 60 years, was referred in good time and hence had sufficient time to consider domiciliary ventilation. Following the placement of a PEG he started NIPPV electively. In patients with ALS, domiciliary ventilation should be discussed early in the course of the disease. Advance directives with regard to domiciliary ventilation are important, not only to avoid undesired (invasive) ventilation, but also with respect to the placement of a PEG and the appropriate use of oxygen and morphine.

Age-related changes in human thyroarytenoid muscles: a histological and histochemical study.

We examined the thyroarytenoid muscles of 23 larynges in order to assess function-related characteristics and to discover age-related changes. The neonatal thyroarytenoid muscle differed from limb muscles in the slow maturation of fibre types. In adults, we examined the medial part of the thyroarytenoid muscle. It showed a larger variation in fibre size and more endomysial connective tissue than is common for limb muscles. Structural and histochemical evidence of ageing developed from approximately the 6th decade. It comprised a marked increase of endomysial connective tissue and striking myopathic changes of muscle fibres. Up to 20% of the muscle fibres showed at some places of some sections evidence of mitochondrial accumulations and increased mitochondrial enzyme activity (ragged red fibres). The rise of such ragged red fibres is commonly related to the development of mutations in mitochondrial DNA. Significant myopathic changes including mitochondrial abnormalities develop in the thyrovocalis muscle with age and may play a role in the functional deficit of the larynx in old age.

The central nervous system in systemic lupus erythematosus. Part 1. Clinical syndromes: a literature investigation.

OBJECTIVES: To establish the central nervous system (CNS) manifestations of systemic lupus erythematosus (SLE) as described in the literature and to compare the results with two previously published classifications. METHODS: Using PUBMED, a systematic search was performed for publications from 1980 onwards on CNS syndromes of patients with SLE. A distinction was made between CNS syndromes induced by SLE and the CNS autoimmune diseases associated with SLE. Criteria were defined for inclusion of CNS syndromes or diseases as SLE-induced or SLE-associated. RESULTS: The literature search yielded names of 30 syndromes and two diseases, but only 16 syndromes and one disease fulfilled the set of predefined criteria. Two syndromes-depression and anxiety-were predominantly psychological in origin in most patients; other syndromes were biological. DISCUSSION: Strengths and weaknesses of two classifications of CNS syndromes are evaluated. The older of the two is long and has not been accepted fully. Brevity is an advantage of the American College of Rheumatology (ACR) nomenclature system. A disadvantage of this system is the concealment of differences in health risks by the pooling of items. Furthermore, the items of the system do not all belong to the same dimension: one is pathological and the others are clinical. To remedy these drawbacks, we suggest the rephrasing and subdivision of items and that the predominantly psychopathological syndromes should be dealt with separately in epidemiological studies. CONCLUSIONS: SLE may induce 16 different clinical syndromes of the CNS and is occasionally associated with one other CNS autoimmune disease. A modification of the ACR nomenclature system is proposed.

The central nervous system in systemic lupus erythematosus. Part 2. Pathogenetic mechanisms of clinical syndromes: a literature investigation.

OBJECTIVES: To identify the pathogenetic mechanisms of central nervous system (CNS) syndromes of systemic lupus erythematosus (SLE) as described in the literature. METHODS: Using PUBMED, we performed a systematic search of publications from 1980 onwards. Studies were eligible if they had been performed on patients or material from patients with CNS manifestations and definite SLE and when the CNS manifestations were not secondary. Criteria were formulated for the identification of pathogenetic mechanisms. RESULTS: The single most important cause of the CNS syndromes of SLE is ischaemia due to narrowing or occlusion of small vessels, arteries and veins. Antiphospholipid antibodies and premature atherosclerosis play roles in these processes, but they have not been delineated definitely. Intracranial and intraspinal haemorrhages are much less frequent than ischaemia and are presumably in part due directly to SLE. Vasculitis may cause ischaemia or haemorrhage in the CNS and is involved occasionally, as shown by imaging and histological findings. White matter damage is heterogeneous and ill-understood. It includes white matter degeneration and myelin vacuolation of the spinal cord, and reversible leucoencephalopathy due to oedema. Antibody-induced neuronal dysfunction in the CNS is a realistic hypothesis and may involve anti-ribosomal P antibodies and several other antibodies. Deficiency of psychological reactions forms a separate and entirely different category of mechanisms. CONCLUSIONS: Causes have been identified or possible causes have been suggested for most of the CNS syndromes of SLE, thus offering rationales for different forms of prevention and therapy.

Diagnostic and classification criteria for the Guillain-Barré syndrome.

BACKGROUND: Diagnostic criteria for the Guillain-Barré syndrome (GBS) have been available since 1978. Since then, several variants have been described. More recently, a distinction has been made between pure motor forms, severe sensory forms, primary axonal and primary demyelinating varieties. Associations of clinical characteristics, and specific infections and the presence of antiganglioside antibodies have been found. For further studies on GBS, it is therefore necessary to reconsider the available diagnostic criteria and add additional criteria for subclassification. METHODS: A panel of (20) experts was formed. The literature representing the recent developments in GBS subclassification was reviewed. Following a consensus protocol, diagnostic and classification criteria were formulated. RESULTS: The diagnosis of GBS can usually be made on clinical characteristics. A schedule for subclassification has been made to cover also the clinical variants in a systematic manner.

Epidemiology of inclusion body myositis in the Netherlands: a nationwide study.

Epidemiologic data on inclusion body myositis (IBM) are scarce, and possibly biased, because they are derived from larger neuromuscular centers. The present nationwide collaborative cross-sectional study, which culminated on July 1, 1999, resulted in identification of 76 patients with IBM and the establishment of a prevalence of 4.9 patients with IBM per million inhabitants in the Netherlands. Several discrepancies suggest that this may be an underestimation. The most frequently identified pitfall in diagnosing IBM was an erroneous diagnosis of polymyositis or motor neuron disease.

A novel gamma-sarcoglycan mutation causing childhood onset, slowly progressive limb girdle muscular dystrophy.

Limb girdle muscular dystrophy is a heterogeneous group of disorders. One autosomal recessive subtype, LGMD2C, has been linked to chromosome 13, and is caused by gamma-sarcoglycan deficiency in muscle. This report describes a novel missense mutation identified in a large consanguineous Dutch family with LGMD. This mutation leads to reduction of gamma-sarcoglycan, and gives rise to a childhood-onset, slowly-progressive dystrophy.

The heart in limb girdle muscular dystrophy.

OBJECTIVE: To assess the frequency, nature, and severity of cardiac abnormalities in limb girdle muscular dystrophy, and its relation to age and weakness in various genotypes. DESIGN: In 26 autosomal dominant, 38 autosomal recessive, and 33 sporadic strictly defined patients with limb girdle muscular dystrophy, cardiac evaluation included history, physical examination, chest x ray, electrocardiography, 24 hour ECG Holter monitoring, and echocardiography. In 35 of the 71 autosomal recessive and sporadic cases muscle biopsies were available for sarcoglycan analysis. MAIN RESULTS: Dilated cardiomyopathy was present in one autosomal dominant case and in three advanced autosomal recessive or sporadic patients, of whom two were found to have alpha sarcoglycan deficiency. Two of these three patients and three other cases showed ECG abnormalities known to be characteristic of the dystrophinopathies. A strong association between the absence of alpha sarcoglycan and the presence of dilated cardiomyopathy was found (p = 0.04). In six autosomal dominant cases there were atrioventricular (AV) conduction disturbances, increasing in severity with age and in concomitant presence of muscle weakness. Pacemaker implantation was necessary in four. CONCLUSIONS: 10% of these patients had clinically relevant cardiac abnormalities. In autosomal dominant limb girdle muscular dystrophy one subtype characterised by muscle weakness and AV conduction disturbances is recognised. In the course of autosomal recessive/sporadic limb girdle muscular dystrophy, dilated cardiomyopathy may develop, probably related to deficiency of dystrophin associated proteins.

[Peer review in requests for subsidy]. / Peer review bij aanvragen voor subsidie.

There is peer review by scientific journals and by fund granting institutions. The former is usually a very thorough procedure with the authors being informed of the reasons for rejection of the article, whereas the latter often leaves the applicants with doubts as to the thoroughness and the fairness of the procedure. It is suggested that grant peer review follow the rules for scientific journal peer review including information of the applicants of the referees' findings and opinions. Moreover there is a need for an ombudsperson to deal with complaints.

Intermittent cyclophosphamide and prednisone treatment of polyneuropathy associated with monoclonal gammopathy of undetermined significance.

In an open prospective study, we analyzed the effect of cyclophosphamide (300 mg/m2 body surface daily for 4 days) combined with prednisone (40 mg/m2 body surface daily for 5 days) at 4-week intervals during 6 months in 16 patients with polyneuropathy associated with monoclonal gammopathy of undetermined significance (MGUS). Eleven patients had an IgM-MGUS and five an IgG-MGUS. During a follow-up period of 3 years, eight patients had improvement and six patients stabilized, based on quantitative neurologic examination, the Rankin disability scale, and electrophysiologic studies. These 14 patients had neuropathy with demyelinating and axonal features. One patient with a purely axonal neuropathy had deterioration despite therapy. One other patients developed severe leukopenia as side effect of cyclophosphamide, necessitating withdrawal of treatment. A difference in response was not present in patient with IgM- or IgG-MGUS, nor in patients with or without autoantibodies against myelin-associated glycoprotein. Nine patients had a bone marrow biopsy before and 1 year after treatment. In eight patients, the monoclonal lymphoid IgM or plasma cell IgG infiltration decreased, while in four the monoclonality disappeared after treatment. In the patient who had neurologic deterioration, repeated bone marrow biopsy showed deposits of amyloid. In conclusion, short-term treatment with intermittent cyclophosphamide and prednisone may have a long-term favorable effect in patients with demyelinating polyneuropathy associated with MGUS.

The clinical spectrum of limb girdle muscular dystrophy. A survey in The Netherlands.

A cross-sectional study was performed in the Netherlands to define the clinical characteristics of the various subtypes within the broad and heterogeneous entity of limb girdle muscular dystrophy (LGMD). An attempt was made to include all known cases of LGMD in the Netherlands. Out of the reported 200 patients, 105 who fulfilled strictly defined criteria were included. Forty-nine patients, mostly suffering from dystrophinopathies and facioscapulohumeral muscular dystrophy, appeared to be misdiagnosed. Thirty-four cases were sporadic, 42 patients came from autosomal recessive and 29 from autosomal dominant families. The estimated prevalence of LGMD in the Netherlands was at least 8.1 x 10(-6). The clinical features of the autosomal recessive and sporadic cases were indistinguishable from those of the autosomal dominant patients, although calf hypertrophy was seen more frequently, and the course of the disease was more severe in autosomal recessive and sporadic cases. The pectoralis, iliopsoas and gluteal muscles, hip adductors and hamstrings were the most affected muscles. Distal muscle involvement occurred late in the course of the disease. Facial weakness was a rare phenomenon. The severity of the clinical picture was correlated with a deteriorating lung function. All autosomal dominantly inherited cases showed a mild course, although in two families life-expectancy was reduced because of concomitant cardiac involvement.

Two divergent types of nerve pathology in patients with different P0 mutations in Charcot-Marie-Tooth disease.

In seven unrelated patients with a demyelinating motor and sensory neuropathy, we found mutations in exons 2 and 3 of the P0 gene. Morphologic examination of sural nerve biopsy specimens showed a demyelinating process with onion bulb formation in all cases. In four patients, ultrastructural examination demonstrated uncompacted myelin in 23 to 68% of the myelinated fibers, which is in agreement with the widely accepted function of P0 as a homophilic adhesion molecule. Three patients showed normal compact myelin, but morphology was dominated by the abundant occurrence of focally folded myelin. The two divergent pathologic phenotypes exemplify that some mutations act differently on P0 protein formation or function than others, which is probably determined by site and nature of the mutation in the P0 gene.

Effects of ciliary neurotrophic factor on retrograde cell reaction after facial nerve crush in young adult rats.

Locally applied ciliary neurotrophic factor (CNTF) has a powerful effect on retrograde axonal reaction following facial nerve crush in neonatal rats. We examined whether it also exerts a strong effect on retrograde axonal reaction in young adult rats when administered subcutaneously. The dose was 1 mg/kg body weight, three times a week, similar to that used in a previous experiment in which CNTF was reported to have an effect. We studied changes in the morphology of the motor nerve cell bodies, in the number of perineuronal microglial cells and in the expression of five proteins. It appeared that CNTF prevented swelling of the facial motoneuron cell bodies but it did not influence the swelling of the nucleus nor the shift of the nucleus towards the periphery. In saline-treated rats, facial nerve crush resulted from day two to day six in a marked increase in the number of perineuronal glial cells. This increase was neither diminished nor augmented by CNTF. Following facial nerve crush, the immunoreactivity of the proteins C3bi, GFAP, B-50 and CGRP increased in the glial cells and motoneuron cell bodies, whilst the immunoreactivity of synaptophysin at the membrane of the motoneuron cell bodies decreased. CNTF had no obvious effect on these changes. It was concluded that in young adult rats under the present conditions, CNTF had only a small effect on a specific aspect of the retrograde cell reaction. The small effects might be explained by the minor availability of CNTF to the motoneuron cell bodies. The gain in body weight of rats treated with CNTF was less than that of saline-treated rats.

Genetic heterogeneity of hereditary motor and sensory neuropathy type VI.

Charcot-Marie-Tooth disease comprises a heterogeneous group of neurologic disorders that shape peripheral motor and sensory neuropathy. A classification of these disorders was proposed in 1975, defining seven types of hereditary motor and sensory neuropathy. Clinical features of hereditary motor and sensory neuropathy type VI are muscle weakness and atrophy in leg and hand muscles, leading to progressive disability and loss of vision and progressing to blindness due to optic atrophy. Hereditary motor and sensory neuropathy type VI was first reported in 1879 by Vizioli, who described a kinship in which a father and two sons presented with peroneal muscular atrophy in association with optic atrophy. Since then, at least nine similar cases have been reported: three sporadic cases, two pairs of siblings who were offspring of consanguineous parents, and one pair of siblings who were offspring of unrelated parents suggesting autosomal recessive inheritance. Vertical transmission has been reported only by Vizioli. We present a father and two offspring (one boy and one girl) with the above-mentioned characteristic features of hereditary motor and sensory neuropathy type VI. Vizioli's kinship and either an autosomal recessive or autosomal dominant pattern of inheritance.