Effect of deep brain subthalamic stimulation on camptocormia and postural abnormalities in idiopathic Parkinson's disease.

Camptocormia has been described in patients with idiopathic Parkinson's disease (PD). We present a patient with young-onset PD in whom the disease progressed over 25 years to a crippling state with severe camptocormia and bent knees. The camptocormia along with other parkinsonian symptoms improved dramatically after bilateral subthalamic deep brain stimulation.     

Histopathological analysis of skeletal muscle in patients with Parkinson's disease and ‘dropped head’/‘bent spine’ syndrome

Background‘Dropped head’ and ‘bent spine’ phenomena are recognized clinical presentations of neuromuscular disorders. Similar symptoms are known in patients with parkinsonian syndromes, but their pathophysiology remains unclear. One hypothesis is a relation between the movement disorder and the skeletal muscle pathology.MethodsWe describe detailed histopathological data from 19 consecutive skeletal muscle biopsies in patients with idiopathic Parkinson's disease (PD) and concomitant ‘dropped head’ or ‘bent spine’ syndrome. A biochemical analysis of the respiratory chain complexes was also performed, and clinical, electrophysiological, and imaging data were analyzed.ResultsThe subjects developed neuromuscular symptoms 2.7 ± 2.4 years after onset of PD. We found no correlation with the age at onset of the disease, disease duration, or severity. We found no evidence for dystonia nor did we find any relationship between their anti-parkinsonian medication, and possible drug side effects. Muscle biopsies were abnormal in all patients. Based on histopathological criteria we divided the muscle pathology into three different groups, i.e. necrotizing myopathy, inflammatory myopathy, and myopathy with mitochondrial abnormalities. Biochemical analysis of respiratory chain complexes revealed abnormalities in nine patients.Conclusions‘Dropped head’ and ‘bent spine’ symptoms in association with PD appear to be accompanied by a wide spectrum of histopathological abnormalities in skeletal muscle. A muscle biopsy should be performed to identify potentially treatable conditions (i.e. inflammatory myopathies).     

Employment of patients with multiple sclerosis among the population of Lód?

The studied material comprised multiple sclerosis patients aged 46 years or less, not staying in welfare institutions, with at least 5 years of the disease, recorded as cases of this disease 5-6 years previously during one year (Oct 1 1973 to Nov 31 1974) in neurological outpatient clinics or hospital departments of neurology or neurosurgery. The percent of those working in gainful occupations was 26%, and in the subgroup of cases with least pronounced disease it was 43%, while only 10% of all patients were outworkers. Only 4 patients were studying in schools. In the subgroup of patients who were unable to use municipal transport means, even with assistance of other persons, none was working. Only half those patients, who were not working despite full of nearly full motor fitness, declared their willingness to work, among them were 5 out of 6 men only 11 out of 26 women. Eight patients tried to get jobs without success. These facts indicate a negative attitude towards occupational work in a fairly large part of the patients and their families, and also failing organization of employment of disabled persons.     

Bent spine syndrome as the initial symptom of late‐onset Pompe disease

Introduction: Late‐onset Pompe disease (LOPD) is a rare disorder characterized by progressive proximal muscle weakness and early respiratory insufficiency, for which enzyme replacement therapy (ERT) is available. Methods: Having diagnosed a case of LOPD presenting with bent spine syndrome, we conducted a brief survey in the French centers involved in management of Pompe disease, from which we collected data on 3 other cases. Results: The patients (3 women and 1 man) had a mean age of 64 years (range 51–77 years) and a delay in diagnosis of approximately 10 years (range 8–42 years). At diagnosis, 3 patients already had respiratory symptoms. All had normal or very mildly raised creatine kinase levels and magnetic resonance imaging abnormalities in the paraspinal muscles. They exhibited the most frequent mutation in Pompe disease (c.‐32‐13 T>G). Conclusion: Clinicians should be aware of this atypical presentation of LOPD to enable earlier diagnosis and treatment. Muscle Nerve 56 : 167–170, 2017     

SOCIAL ASPECTS IN MYASTHENIA GRAVIS

The myasthenics in Finland (n = 240) have been registered and treated in one center for more than 10 years. Of this material, an investigation was performed of their medico-social state as of 1 January, 1975. The study comprised 88 per cent (210) of the patients. In the working age (16–64 years) were 181 patients. Compared to the total Finnish population, the myasthenic patients lived more often in urban districts, had had more intermediate-school and university-but less vocational-school education, and belong as a whole to "higher" social classes. The severity and the variability of the disease naturally influenced the disability. A change from severe to slight symptoms occurred in 38 per cent, and 12 per cent of the myasthenics were in complete remission (% of whom had had severe symptoms). One third (72) got a full pension because of myasthenia, and about one tenth (25) because of some other reason. Of these who got a full pension for myasthenia, 7 per cent were in complete remission without any myasthenic symptoms. The influence of thymectomy on the degree of disability was impressive, since more than 50 per cent of disabled myasthenic patients returned to work thereafter. Thus, because of the unpredictable, but on the long term quite favourable course, a full pension should not be prescribed early (during the first 5 years) of the disease. An active treatment may also change the outlook for even the most severely disabled patients.     

Parkinson's disease, progressive lumbar kyphosis and focal paraspinal myositis

INTRODUCTION: The camptocormia (bent spine) is characterized by a severe forward flexion of the thoracolumbar spine which disappears in the supine position. Clinical case. We describe a typical case observed in a parkinsonian patient. The MRI, electromyogram and biopsy of the paraspinal muscles revealed a typical myositis pattern. DISCUSSION: This case, the sixth published to our knowledge, confirms that focal myositis is associated with the camptocormia in Parkinson's disease. Typically it is observed in male subjects, appearing 4 to 6 years after the onset of Parkinson's disease, in fluctuating patients treated by an association of L-Dopa and agonist. It appears quickly and becomes the most important symptom. Antiparkinsonian drugs are useless. CONCLUSION: This exceptional picture raises original pathophysiological and therapeutic questions. Systematic studies should be performed in order to detail the pathophysiological link between these 3 entities: Parkinson's disease, focal myositis and camptocormia.     

Long-term results of tacrolimus in cyclosporine- and prednisone-dependent myasthenia gravis

Seventy-nine patients with cyclosporine- and prednisone-dependent myasthenia gravis (MG) after thymectomy received tacrolimus for a mean of 2.5 +/- 0.8 years. Prednisone was withdrawn in all but two patients. Anti-acetylcholine antibodies and MG score for disease severity decreased significantly and muscular strength increased by 39%. Complete stable remission was achieved in 5% of patients and pharmacologic remission in 87.3%. All patients resumed full activities of daily living.     

Axial myopathy – an unrecognised entity

Axial myopathy (AM) is a rare neuromuscular disorder characterised by selective involvement of the spinal muscles with a bent spine and/or drooping head as leading clinical features. We here report the results of clinical, histopathological, MRI, molecular genetics and electrophysiological investigations carried out on six patients affected by pure axial myopathy. Symptoms appeared within an age range of 35 to 56 years. The first symptoms were difficulty in keeping the trunk and head in an upright position. Both bent spine and dropped head were reduced in a supine position. The disease was slowly progressive. Muscle strength examination and muscle imaging revealed involvement of the spinal and neck extensor muscles only. Serum CK was normal to slightly increased. EMG and muscle biopsy specimens obtained from spinal muscles showed an advanced chronic myopathic pattern. We conclude that axial myopathy may be much more common than previously thought, because gradual progression of cervical kyphosis may often be explained as a feature of normal ageing or as an associated sign of several neurological disorders and vertebral degeneration diseases. Received: 24 June 2001, Received in revised form: 2 November 2001, Accepted: 6 November 2001     

Subacute sclerosing panencephalitis (SSPE) the story of a vanishing disease

Subacute sclerosing panencephalitis (SSPE), is a devastating "slow virus" brain disease which affects young children who had measles some 6-7years earlier. Although, the pandemic of SSPE during 1960-1980's was almost eradicated due to mass immunization, the disease is still taking the life of young children in countries where measles immunization is incomplete and in world regions where genetic polymorphism to this particular infection is present. The present review was written for the fortunate young generation of pediatricians and pediatric neurologists who probably have not seen a case of SSPE during their career, and for those who work in counties where the disease has not been eradicated. It is also a reminder that with full coverage of measles immunization this devastating disease can be fully eradicated.     

Quality of life in Polish patients with long-lasting Parkinson's disease.

The objective of this study was to evaluate possible relationships between quality of life (QoL) of Polish patients with long-lasting Parkinson's disease and various demographic and clinical factors. The study comprised 141 patients of Movement Disorders outpatient clinics in Warsaw and Gdansk with at least 5 years of the disease duration. Mean age of patients was 68.09 +/- 8.51 years, mean duration of disease was 11.87 +/- 5.14 years. To assess the quality of life, the Parkinson's Disease Questionnaire (PDQ-39) was used. Additional questions concerned duration of disease, initial and current treatment and expenses associated with therapy. Self-perceived symptoms of depression were in our study the most important factor determining QoL. Duration of the disease and expenses related to the treatment also have a significant impact on the QoL. Patient's age and presence of dyskinesia seem to be irrelevant to the quality of life.     

Clinical course in young patients with sporadic Creutzfeldt-Jakob disease

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disease with the greatest incidence occurring in patients between 60 and 70 years old. Younger patients may also be affected. In this study, we used all case material available from 52 patients with sCJD aged 50 years or younger at disease onset, who were identified between 1993 and 2003 in Germany. The objective of this study was to describe the psychiatric and neurological features of these young patients with emphasis on the different codon 129 genotypes and PrP types, and to compare them with elder patients with sCJD and patients with variant CJD. We also gave particular attention to electroencephalogram, magnetic resonance imaging, and 14-3-3 results, as well as to the neuropathological lesion profile. The clinical syndrome in young patients differs from elder patients with CJD with respect to clinical signs, disease duration, technical investigations, and neuropathological lesion profile. The psychiatric symptoms in young patients with sCJD are similar to the psychiatric symptoms expressed by patients with variant CJD; however, in contrast with the variant cases, young patients with sCJD experience development of prominent dementia early in the disease course.     

Dyssynergia cerebellaris myoclonica (Ramsay Hunt syndrome): a condition unrelated to mitochondrial encephalomyopathies.

Thirteen patients with dyssynergia cerebellaris myoclonica (Ramsay Hunt syndrome) had full clinical and neurophysiological study as well as muscle biopsy. The patients had action myoclonus, generalised epileptic seizures, and mild cerebellar syndrome. The disease was inherited in an autosomal recessive pattern in five patients, and occurred as isolated cases in the remaining eight patients. The age at onset of symptoms ranged from 6 to 15 years (mean, 10.4 years). The EEG and polygraphic findings included normal background activity in most patients, spontaneous fast generalised spike-and-wave discharges, photosensitivity, no activation during slow sleep, and vertex and rolandic spikes in REM sleep. Results of muscle biopsy, performed an average of 14 years after onset of the disease, were normal and showed no mitochondrial abnormalities. These findings suggest that Ramsay Hunt syndrome is a condition with distinctive clinical and neurophysiological features and unrelated to mitochondrial encephalomyopathies.     

Transferrin in patients with multiple sclerosis: a comparison among various subgroups of multiple sclerosis patients

OBJECTIVES: To compare cerebrospinal fluid (CSF) and serum transferrin (Tf) concentrations, transferrin quotient and index in various subgroups of MS patients. MATERIAL AND METHODS: CSF and serum transferrin concentrations, transferrin quotient QTf (i.e. CSF transferrin/serum transferrin x 10(3)) and index (QTf/Qalbumin) were determined in a group of 51 patients with clinically definite or probable multiple sclerosis (MS). Patients were subdivided according to the disease form (relapsing-remitting = RR, secondary progressive = SP, primary progressive = PP; patients with RR form were further subdivided into those in the attack and those in remission), disease severity (EDSS 0-5.5, EDSS 6.0-10.0), its treatment (non-treated - including patients treated with vitamins and/ or vasodilators only, treated - i.e. glucocorticoids and/or immunosuppressants and/or (exceptionally) beta-interferon), disease duration (0-2 years, >2-10 years, > 10 years) and sex. Correlation of transferrin values with age was also performed. RESULTS: Serum transferrin was somewhat lower and significantly more frequently subnormal in PP patients in comparison with the SP form and the RR form in remission. Transferrin index was significantly higher in the PP form than in the RR as well as the SP form. Transferrin quotient was significantly more frequently subnormal in patients in remission compared to those in the attack of the RR disease. CSF transferrin as well as transferrin quotient were more frequently subnormal in patients with short disease duration (0-2 years) than in patients with longer disease duration; these parameters, however, correlated also significantly with age. CSF transferrin and transferrin quotient were higher in male than in female patients. CONCLUSION: The authors conclude that evaluation of transferrin in MS patients - along with albumin - may help to differentiate among various MS subgroups, since there are significant differences among RR, SP and PP forms. For this purpose, however, other CSF protein fractions should be evaluated in parallel in order to obtain more complex information and to establish a panel of examinations enabling multiple statistical analyses. Transferrin evaluation in MS may also be of significant theoretical interest, since transferrin is known to be involved in the regulation of iron metabolism and it may have a protective role against the oxidative stress. Moreover, transferrin is a growth factor important for proliferation of activated T lymphocytes. By means of the use of transferrin quotient and especially transferrin index, it may be possible to estimate the proportion of intra-CNS-synthesized transferrin and/or rate of specific transferrin transport across the blood-CSF barrier. Further studies are, however, needed for such an evaluation.     

HLA-DRB1 and disease outcome in multiple sclerosis

The association between susceptibility to multiple sclerosis (MS) and the class II MHC allele HLA-DRB1*15 is well established although a possible relationship between this allele and outcome in MS is less clear. HLA-DRB1 typing was performed on 375 unrelated white patients with clinically definite MS and on 367 healthy controls. Putative associations of the gene with outcome were examined by dividing patients into two groups: those with an EDSS of 0-5.5 (mild/moderate disease) and those with an EDSS of 6-10 (severe disease). In order to minimise the effects of disease variability patients with a disease duration of at least 10 years or 15 years were examined. As subsidiary HLA-DRB1*03 and HLA-DRB1*04 associations have been previously reported, the effect of these alleles was also examined. As expected, HLA-DRB1*15 was found more frequently in patients than in controls (P < 0.000001). HLA-DRB1*15 positive patients had a significantly earlier age at onset than HLA-DRB1*15 negative patients. No significant associations were noted between HLA-DRB1*15 and outcome in the total patient group or in patients with a disease duration of 10 years or longer. In patients with a disease duration of at least 15 years HLA-DRB1*15 negative status was associated with a worse prognosis, although this did not remain significant after correction for multiple testing. It is thus likely that the contribution of HLA in MS is primarily towards onset and initial triggering mechanisms rather than influencing disease progression, chronicity and severity.     

DNA testing for Huntington disease in the Turkish population

Huntington disease (HD) is an autosomal dominant inherited disease, characterized by involuntary movements, behavioral and personality changes and dementia. Although the mean age at onset is about 40 years, onset varies from 5 to 79 years. Therefore, at-risk individuals are never sure to have escaped the disease. The genetic defect is a CAG trinucleotide repeat expansion at the 5' end of the IT-15 gene on chromosome 4. In this study, we analyzed 127 patients with HD and 122 healthy controls. The numbers of CAG repeats varied from 38 to 78 (median: 42) in 127 HD patients, while in healthy controls we observed only 10-35 CAG repeats (median: 18). The length of the CAG repeat expansion in Turkish HD patients and normal controls was similar to that reported from other populations. Negative correlations (r = -0.67) were also found between age of disease onset and repeat length.     

Mean platelet volume in patients with metabolic syndrome and its relationship with coronary artery disease

BACKGROUND: Mean platelet volume (MPV) is an indicator of platelet activation which is a central process in the pathophysiology of coronary heart disease. The metabolic syndrome (MS) is characterized as the clustering of closely associated and interdependent atherosclerotic risk factors. MS has also been shown to be strongly associated with poor outcome in patients with coronary artery disease (CAD). The present study was designed to investigate MPV values in patients MS and to interrogate the association with CAD. METHODS: We measured MPV in 205 consecutive patients with metabolic syndrome (mean age, 53+/-7 years) and 140 control subjects without metabolic syndrome (mean age, 52+/-6 years). All patients were selected from individuals who underwent coronary angiography in our hospital with a suspicion of coronary artery disease. To evaluate the severity of coronary artery disease, the patients with MS were subdivided depending upon the coexistence of coronary artery disease: normal coronary arteries, having coronary stenotic lesions of <50%, and having coronary stenotic lesions of >50%. RESULTS: The MPV was significantly higher in patients with MS than in the control group (10.19+/-1.49 fl vs 8.21+/-1.02 fl, p<0.001). According to the CAD severity, there were no statistically significant differences in MPV among these subgroups. CONCLUSION: We have shown for the first time that patients with MS have higher MPV compared to control subjects with normal coronary angiograms and to be associated with CAD. Hence MPV can be used as a follow up marker in patients with MS in the point of CAD.     

Lisuride in de novo Parkinsonian patients: a four-year follow-up

Lisuride at a mean daily dose of 3.2 mg was given to 15 untreated idiopathic Parkinson's disease patients. There were 10 dropouts, due mainly to inefficacy in the first months of therapy. The parkinsonian pattern in the patients who remained in the study for the full 4 years showed distinct improvement, which was maintained for less than 2 years. The patients did not develop "on-off" phenomena or abnormal involuntary movements during follow-up.     

Association between amantadine and the onset of dementia in Parkinson's disease.

The objective of this study is to compare the occurrence of dementia among Parkinson's disease (PD) patients treated with amantadine (AM group) with those never exposed to it (NoAM group). PD dementia shares neuroanatomical and biochemical similarities with Alzheimer's disease (AD). Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist has been shown to be beneficial in AD. Memantine is a dimethyl derivative of amantadine, which also possesses NMDA receptor blocking properties. We hypothesized that amantadine could have a beneficial effect on the occurrence of PD dementia. PD patients attending the Movement Disorders Clinics in Hillel Yaffe, Asaf Harofe Medical Centers (Israel) and Pisa (Italy) were included. Taking the onset of dementia as the endpoint, survival curves for AM and NoAM patients were estimated by the Kaplan-Meier method. The study population consisted of 593 patients (age, 69.5 +/- 9.9 years; PD duration, 9.2 +/- 6.0 years; 263 patients (44%) amantadine treated). The endpoint of dementia was reached by 116 patients (20%). PD duration until dementia was significantly longer for AM patients (9.1 +/- 5.7 years) than for NoAM patients (5.9 +/- 4.6 years, P = 0.006). The duration of amantadine exposure positively correlated with PD duration until dementia (P = 0.0001). Survival analysis, taking dementia onset as endpoint, showed slower mental decline in AM patients (Log rank P = 0.0049, Wilcoxon P = 0.0024). Mini-Mental State Examination scores were significantly higher for AM patients than for the NoAM group (P = 0.01). Age of PD onset also significantly influenced the duration of PD until dementia. Amantadine use may delay the onset of dementia in PD patients and may attenuate its severity.     

Sublingual administration of apomorphine in the treatment of motor fluctuations in Parkinson disease]

Apomorphine, a mixed dopaminergic agonist was given sublingually to 12 patients with Parkinson's disease disabled by severe on-off fluctuations. The patient's mean age was 57 years and the duration of Parkinson's disease was 12 years. All patients were also given domperidone (60 mg/day). Apomorphine was administered as soon as the off periods appeared. On periods were observed in 11 patients, with a mean apomorphine dose of 40 mg for each administration (extremes values: 20-60 mg). One patient had no motor benefit after an apomorphine dose of 120 mg. The mean duration of daily off periods was reduced by 64 per cent in 11 patients, for a mean duration of 8 months (extremes values: 2-12 months). Four patients developed stomatitis or gingival edema and stopped treatment. This pilot study shows that sublingual apomorphine, during a mean period of 8 months, significantly decreases off periods in parkinsonian patients. Others studies are necessary to confirm these results.