Espen Dietrichs

Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson's disease

To summarize the 2010 EFNS/MDS‐ES evidence‐based treatment recommendations for the management of Parkinsons disease (PD). This summary includes the treatment recommendations for early and late PD.

Is lectin-coupled horseradish peroxidase taken up and transported by undamaged as well as by damaged fibers in the central nervous system?

Uptake and transport of horseradish peroxidase-wheat germ agglutinin conjugate (HRP-WGA) in intact and damaged passing fibers were studied by injections of the medulla and pons in 11 cats. Injections with evidence of damage to olivocerebellar fibers and cranial nerve fibers invariably lead to retrograde labeling of neurons in the inferior olive and cranial motor nuclei. With staining around--but apparently no damage of--cranial nerve root fibers, no labeling was found in their motor nuclei. Injections limited to the medullary pyramid with slight fiber damage and limited staining lead to faint retrograde labeling of a small number of cells in the ipsilateral sensorimotor cortex. More extensive staining and fiber damage of the pyramid gave a higher number of labeled cells in the ipsilateral sensorimotor cortex. From these experiments we conclude that HRP-WGA is taken up and transported retrogradely with subsequent significant cell labeling in damaged but not in intact fibers. Anterograde transport of HRP-WGA in fibers passing through the injected area was found to take place only for a very short distance, as judged from cases with injections of either the pons or the medullary pyramid interrupting many corticospinal fibers.

The cerebellar-hypothalamic axis: basic circuits and clinical observations.

Experimental studies on a variety of mammals, including primates, have revealed direct and reciprocal connections between the hypothalamus and the cerebellum. Although widespread areas of the hypothalamus project to cerebellum, axons arise primarily from cells in the lateral, posterior, and dorsal hypothalamic areas; the supramammillary, tuberomammillary, and lateral mammillary nuclei; the dorsomedial and ventromedial nuclei; and the periventricular zone. Available evidence suggests that hypothalamocerebellar cortical fibers may terminate in relation to neurons in all layers of the cerebellar cortex. Cerebellohypothalamic axons arise from neurons of all four cerebellar nuclei, pass through the superior cerebellar peduncle, cross in its decussation, and enter the hypothalamus. Some axons recross the midline in caudal areas of the hypothalamus. These fibers terminate primarily in lateral, posterior, and dorsal hypothalamic areas and in the dorsomedial and paraventricular nuclei. Evidence of a cerebellar influence on the visceromotor system is presented in two patients with vascular lesions: one with a small defect in the medial cerebellar nucleus and the other with a larger area of damage involving primarily the globose and emboliform nuclei. Both patients exhibited an abnormal visceromotor response. The second, especially, showed abnormal visceromotor activity concurrent with tremor induced by voluntary movement. These experimental and clinical data suggest that the cerebellum is actively involved in the regulation of visceromotor functions.

Supportive evidence for 11 loci from genome-wide association studies in Parkinson's disease

Genome-wide association studies have identified a number of susceptibility loci in sporadic Parkinsons disease (PD). Recent larger studies and meta-analyses have greatly expanded the list of proposed association signals. We performed a case-control replication study in a Scandinavian population, analyzing samples from 1345 unrelated PD patients and 1225 control subjects collected by collaborating centers in Norway and Sweden. Single-nucleotide polymorphisms representing 18 loci previously reported at genome-wide significance levels were genotyped, as well as 4 near-significant, suggestive, loci. We replicated 11 association signals at p < 0.05 (SNCA, STK39, MAPT, GPNMB, CCDC62/HIP1R, SYT11, GAK, STX1B, MCCC1/LAMP3, ACMSD, and FGF20). The more recently nominated susceptibility loci were well represented among our positive findings, including 3 which have not previously been validated in independent studies. Conversely, some of the more well-established loci failed to replicate. While future meta-analyses should corroborate disease associations further on the level of common markers, efforts to pinpoint functional variants and understand the biological implications of each risk locus in PD are also warranted.

The cerebellar projection from the lateral reticular nucleus as studied with retrograde transport of horseradish peroxidase

SummaryThe cerebellar projection from the lateral reticular nucleus (NRL) was studied in cats by means of retrograde axonal transport of horseradish peroxidase (the projection to the paramedian lobule was not included, see Brodal, 1975, for afferents to this cortical region). The entire cerebellar cortex and all cerebellar nuclei receive fibres from the NRL. The strongest connection is with the anterior lobe and lobulus VIIIB of the posterior lobe vermis. As concerns the anterior lobe the observations confirm the previous finding by Brodal (1975) that there is a clearcut topical pattern in the nuclear projection to this part of the cerebellum. The observations furthermore show that crus II is the only cerebellar region devoid of fibres from the subtrigeminal part of the NRL.The cerebellar projection from the NRL is bilateral with a heavy ipsilateral preponderance. The large majority of the labeled cells within the NRL are of the small category (<25 μm in size). This and the other findings are discussed in relation to previous studies on the efferent and afferent connections of the nucleus.

Prevalence of primary focal and segmental dystonia in Oslo

All patients seeking medical treatment for primary focal and segmental dystonia in Oslo, Norway, were identified in a service-based prevalence study. A total of 129 patients with focal and segmental dystonia were treated. The total prevalence was 25.4 per 100,000, but the prevalence increased with age from 4.1 (age < 30) to 58.7 (age > 70). The prevalence in subjects of European descent was 28.3 per 100,000, much higher than among first-generation immigrants of Asian and African descent.

A note on the anterograde transport of horseradish peroxidase within the olivocerebellar fibres

SummaryIn cats with unilateral injections of horseradish peroxidase in the inferior olive which were processed according to the Mesulam (1978) technique crossed olivocerebellar fibres can be followed on both sides of the brain stem into the cerebellum to the level of the granular layer. The observations indicate that perikaryal uptake of horseradish peroxidase is not a prerequisite for the visualization of the fine preterminal fibres.

The interconnection between the vestibular nuclei and the nodulus: a study of reciprocity

The reciprocal connections between the nodulus and the vestibular and perihypoglossal nuclei in the cat have been studied by anterograde and retrograde transport after implants of crystalline wheatgerm agglutinin-horseradish peroxidase complex (WGA-HRP) restricted to one or two nodular folia. The findings supplement the previous study by Epema et al. (Neurosci. Lett., 1985, 57: 273-278), who injected WGA-HRP into the vestibular nuclei. In that study, details concerning the nodular origin and termination of the fibres within the reciprocal connections were given; in the present study, details are given concerning the origin and termination of the fibres within the vestibular and perihypoglossal nuclei. Our observations give evidence that the nodulovestibular fibres are distributed to a somewhat larger area than that projecting back to the nodulus. The distribution of the labelled cells and fibres is shown in Fig. 2. Of the 4 main nuclei, it is only the lateral vestibular nucleus which is devoid of a reciprocal connection with the nodulus, while only groups x and z of the minor cell groups are found to have such projections. Of the perihypoglossal nuclei, it is only the nucleus praepositus hypoglossi which appears to be interconnected with the nodulus.

Good long-term efficacy of pallidal stimulation in cervical dystonia: a prospective, observer-blinded study.

Background and purpose:  Deep brain stimulation of the internal globus pallidus (GPi‐DBS) is established as an effective treatment of primary generalised dystonia in controlled studies. In cervical dystonia (CD), only one previous study has reported observer‐blinded outcome assessment of long‐term GPi‐DBS, with 1‐year follow‐up.

Do pontocerebellar fibers send collaterals to the cerebellar nuclei

Three cats received large injections in the pontine nuclei of horseradish peroxidase labeled wheat germ agglutinin. Pontocerebellar axons were stained throughout their length and dense terminal label was present in the granular layer. The cerebellar nuclei, however, contained only a few scattered labeled fibers without a consistent distribution from case to case. If nuclear collaterals from pontocerebellar fibers exist, they appear to be very few and can be expected to give only a very small contribution to the excitatory input to the cerebellar nuclei.