Emil Greve Pedersen

Human anal reflexes.

By perianal electrical stimulation and EMG recording from the external anal sphincter the anal reflex was constantly present in normal subjects. The latency decreased within certain limits with increasing stimulation to an average minimum latency of 50 ms (SD 10.5). There was no difference between the minimum latency in normal subjects and patients with suprasegmental lesions of the CNS. The latency may be prolonged in patients with lesion of the reflex arc. By stimulation over the posterior tibial nerve behind the medial malleolus a reflex reaction could be picked up constantly from the anal sphincter in normal subjects. This reflex had a longer latency but a lower threshold than the reflex reaction from the tibialis anterior muscle. The average minimum latency from the anal sphincter was 93 ms (SD 21.1) and from the tibialis anterior muscle 64 ms (SD 7.9). In the absence of the anal reflex it may be possible to localise the defect to the afferent or efferent parts of the reflex by using types of stimulation. Preliminary studies of spinal shock revealed a perianally elicited anal reflex in all cases, but also a response to peripheral stimulation in some of the cases, more frequently found in the anal sphincter than in the tibialis anterior muscle.

Late-onset myasthenia not on the increase: a nationwide register study in Denmark, 1996-2009.

An increase in late‐onset myasthenia gravis (MG) has been reported. There are few large population‐based studies over longer periods of time reflecting recent developments in MG incidence.

Functional effect of FGF2- and FGF8-expanded ventral mesencephalic precursor cells in a rat model of Parkinson's disease

Ventral mesencephalic (VM) precursor cells are of interest in the search for transplantable dopaminergic neurons for cell therapy in Parkinsons disease (PD). In the present study we investigated the survival and functional capacity of in vitro expanded, primary VM precursor cells after intrastriatal grafting to a rat model of PD. Embryonic day 12 rat VM tissue was mechanically dissociated and cultured for 4 or 8 days in vitro (DIV) in the presence of FGF2 (20 ng/ml), FGF8 (20 ng/ml) or without mitogens (control). Cells were thereafter differentiated for 6 DIV by mitogen withdrawal and addition of serum. After differentiation, significantly more tyrosine hydroxylase-immunoreactive (TH-ir), dopamine-producing neurons were found in FGF2- and FGF8-expanded cultures compared to controls. Moreover, expansion for 4 DIV resulted in significantly more TH-ir cells than expansion for 8 DIV both for FGF2 (2.4 fold; P<0.001) and FGF8 (3.8 fold; P<0.001) treated cultures. The functional potential of the expanded cells (4 DIV) was examined after grafting into striatum of aged 6-hydroxydopamine-lesioned rats. Amphetamine-induced rotations performed 3, 6 and 9 weeks postgrafting revealed that grafts of FGF2-expanded cells induced a significantly faster and better functional recovery than grafts of FGF8-expanded cells or control cells (P<0.05 for both). Grafts of FGF2-expanded cells also contained significantly more TH-ir cells than grafts of FGF8-expanded cells (P<0.05) or control cells (P<0.01). In conclusion, FGF2-mediated pregrafting expansion of primary VM precursor cells considerably improves dopaminergic cell survival and functional restoration in a rat model of PD.

Use of azathioprine for non‐thymoma myasthenia and risk of cancer: a nationwide case–control study in Denmark

To evaluate the association between the use of azathioprine and risk of cancer in patients with non‐thymoma myasthenia gravis (MG) in a nationwide setting.

Risk of non-melanoma skin cancer in myasthenia patients treated with azathioprine.

The association between use of azathioprine and risk of non‐melanoma skin cancer (NMSC) in patients with myasthenia was evaluated in a nationwide setting. Treatment of autoimmune myasthenia frequently involves long‐term exposure to immunosuppressants, including azathioprine. Use of azathioprine increases the risk of NMSC in organ recipients and probably also in patients with other autoimmune disorders. No previous study has specifically investigated the risk of NMSC in myasthenia patients treated with azathioprine.

Identifying Patients with Myasthenia for Epidemiological Research by Linkage of Automated Registers

Background: We validated a new method of identifying patients with incident myasthenia in automated Danish registers for the purpose of conducting epidemiological studies of the disorder. Methods: For residents of a Danish county (population 484,862) in 1993–2008, we identified any hospital contacts coded for myasthenia in a nationwide patient register and any prescriptions for pyridostigmine in the county prescription register. Results from an acetylcholine receptor antibody register were linked to the data. We verified the diagnosis by a review of medical records. Results: Subjects identified in the Patient Register (n = 83) were comparable with individuals found in the Prescription Register (n = 89) with regard to age and gender, but were more often seropositive (83.1 vs. 74.2%). Seropositivity increased to 91.6% by restricting the data to individuals recorded in both Patient and Prescription Registers (n = 71). We found that for subjects identified in both Patient and Prescription Registers the positive predictive value of the register diagnosis was 92.9% (95% confidence interval, CI, 84.3–97.7), the false-positive rate was low (2.8%), and the sensitivity was acceptable (81.2%; 95% CI 71.2–88.8). Conclusions: Our data indicate that this novel approach of combining diagnosis register and prescription register information provides a feasible and valid method to trace incident myasthenia patients for population-based epidemiological studies.

Relation between flexor spasms, uninhibited detrusor contractions and anal sphincter activity.

The time relation between flexor spasms, detrusor contractions and anal sphincter activity was recorded in a consecutive series of 111 patients with hyperreflexic bladder and flexor spasms. In 76 of the patients flexor spasms were preceded by detrusor contractions. The opposite pattern, namely detrusor contractions preceded by flexor spasms, was seen in only nine patients. The anal sphincter activity was generally increased in relation to detrusor contractions in patients with spinal lesions but decreased in patients with cerebral lesions. The treatment of flexor spasms and uninhibited detrusor contractions is discussed on the basis of this mutual relationship.

Screening for late‐onset Pompe disease in western Denmark

Late‐onset Pompe disease (LOPD) is a rare autosomal recessively inherited metabolic myopathy caused by reduced activity of the lysosomal enzyme alpha‐glucosidase. In a previous screening study at two large neuromuscular university clinics in Denmark, three patients with LOPD were identified out of 103 patients screened. No systematic screening has been performed at the other neurological departments in the western part of Denmark. Thus, patients with a diagnosis of unspecified myopathy were screened for LOPD.

Oral Immunosuppressive Treatment of Myasthenia Gravis in Denmark: A Nationwide Drug Utilization Study, 1996-2013

Although immunosuppressants in the treatment of myasthenia have been available for several decades, population‐based studies describing drug utilization in myasthenia patients are scarce. We aimed in this study to describe the treatment of myasthenia in Denmark in more recent years with emphasis on use of oral immunosuppressant agents. We identified a nationwide cohort of incident myasthenia patients in Denmark from 1996 to 2013 and tracked their use of drugs over the entire period using data from nationwide registers. Patients with myasthenia were classified according to utilization of specific immunosuppressants (e.g. prednisolone) as ‘never user’ or ‘ever user’. We used Kaplan–Meier (K‐M) and proportion of patients covered (PPC) curves to describe treatment onset and termination. We identified 928 patients (52% female) with incident myasthenia in the study period. Overall, 638 (69%) were treated with prednisolone and 506 (55%) with azathioprine. Treatment with prednisolone and azathioprine within 2 years of myasthenia diagnosis was initiated in 462 (56%) and 366 (45%). Only one of four myasthenia patients (n = 231) did not receive oral immunosuppressive treatment at any time in the study period. Prednisolone was stopped in most patients, whereas treatment with azathioprine was often continued throughout follow‐up. In conclusion, we found that treatment of myasthenia in Denmark in recent years corresponded well to the expected clinical course of myasthenia and that most patients underwent long‐term immunosuppression.