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Biomedical subjects

J C Möller

Publications and source records attributed to J C Möller.

At least 19 recordsLinked to original sources
PubMed2006

CNS involvement in hereditary neuropathy with pressure palsies (HNPP).

We assessed seven patients with hereditary neuropathy with liability to pressure palsies (HNPP) with 16 electrophysiological tests and cranial MRI for CNS abnormalities. Mean latencies differed between patients with HNPP and controls for the blink reflex, the jaw-opening reflex, and acoustic evoked potentials. MRI abnormalities were observed in four patients. Our study suggests subclinical but functionally relevant CNS myelin damage in HNPP.

Adult↗
PubMed2005

Pharmacotherapy of Parkinson's disease in Germany.

Treatment standards or guidelines have been developed for most features of Parkinson's disease (PD). However, data on the actual treatment that is put into practice are scarce. In 2000, a nationwide survey on the topic of sudden onset of sleep (SOS) in PD was initiated among the members of the German patient support group (deutsche Parkinson-Vereinigung, dPV). A part of this mailed questionnaire survey covering the antiparkinsonian and concomitant medication of the participants is presented here. This study analyses data sets from more than 6,500 PD patients. The mean dopaminergic dose was equivalent to 599 +/- 387 mg levodopa/die. The most frequently administered drugs were levodopa (94.2 %), dopamine agonists (DA) (71.7 %), amantadine (40.1 %), selegiline (27.6 %), entacapone (20.4 %), budipine (12.3 %), and anticholinergics (11.8 %). Costs of pharmacotherapy were estimated to be approximately 399 million/year in Germany. PD drug therapy in general strongly depended on age, disease duration, and the level of care. The treatment guidelines were apparently not consistently followed underlining the need for their continuous propagation throughout the medical community. In addition our data suggest that non-motor symptoms in PD are not adequately treated and that concomitant sedative medication contributes to the occurrence of SOS.

Age Factors↗
PubMed2004

Combination of 'idiopathic' REM sleep behaviour disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT.

REM sleep behaviour disorder (RBD) and olfactory dysfunction are common and very early features of alpha-synucleinopathies, in particular Parkinson's disease. To investigate the hypothesis that these two clinical features in combination are an indicator of evolving alpha-synucleinopathy, olfactory function was assessed in RBD. We studied 30 patients (18 male, 12 female; mean age 48 +/- 14 years, range 19-78 years) with clinical (idiopathic, n = 6; symptomatic, n = 13, mostly associated with narcolepsy) or subclinical (n = 11, associated with narcolepsy) RBD according to standard criteria and 30 age- and gender-matched healthy control subjects using standardized 'Sniffin' Sticks'. RBD patients had a significantly higher olfactory threshold (P = 0.0001), lower discrimination score (P = 0.003), and lower identification score (P = 0.001). Compared with normative data, 97% of the RBD patients had a pathologically increased olfactory threshold, 63% an impaired odour discrimination score, and 63% a decreased identification score. On neurological examination, signs of parkinsonism were newly found in five patients with clinical RBD (not associated with narcolepsy), who usually had a long history of 'idiopathic' RBD. Four of the five patients fulfilled the UK Brain Bank criteria for the clinical diagnosis of Parkinson's disease. The underlying nigrostriatal degeneration of clinical Parkinson's disease was confirmed by I-123-FP-CIT SPECT in one patient and early nigrostriatal degeneration was identified by SPECT in a further two patients with 'idiopathic' clinical RBD out of 11 RBD patients who agreed to undergo SPECT studies. Our study shows that RBD patients have a profound impairment of olfactory function. Five patients with clinical RBD not associated with narcolepsy had clinical or imaging signs of nigrostriatal degeneration. This new clinical finding correlates with the neuropathological staging of Parkinson's disease (stages 1-3) as proposed by Braak. In stage 1, the anterior olfactory nucleus or the olfactory bulb is affected (along with the dorsal motor nucleus of the glossopharyngeal and vagal nerves). In stage 2, additional lesions consistently remain confined to the medulla oblongata and pontine tegmentum, which are critical areas for RBD. Midbrain lesions are found only in stage 3, in particular degeneration of dopaminergic neurons in the substantia nigra pars compacta. Thus, 'idiopathic' RBD patients with olfactory impairment might present with stage 2 preclinical alpha-synucleinopathy. Since narcoleptic patients are not known to have an increased risk of developing parkinsonism, the pathophysiology and clinical relevance of hyposmia in RBD/narcolepsy patients requires further research.

Adult↗
PubMed2004

Nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 are sorted to dense-core vesicles and released via the regulated pathway in primary rat cortical neurons.

Neurotrophins (NTs) play an important role in the modulation of synaptic transmission and in morphological changes in synaptic structures. Although there is agreement that brain-derived neurotrophic factor (BDNF) is sorted to large dense-core vesicles (LDCVs) and released via the regulated secretory pathway, there has been some dispute regarding the mode of secretion of nerve growth factor (NGF) and neurotrophin-3 (NT-3), two structurally related members of the NT family. In this study, we examined the subcellular localization and release characteristics of NGF, BDNF, and NT-3 in adenovirus-infected primary cortical neurons. We found that all members of the NT family colocalized with markers for the endoplasmic reticulum and Golgi within cell bodies and in a punctate manner with a marker for LDCVs within processes. Moreover, their release was triggered by depolarization, indicating that NGF, BDNF, and NT-3 are released via the regulated secretory pathway. When neurons were coinfected with two separate adenoviruses coding for NGF or BDNF, both NTs showed almost complete vesicular colocalization within single cells, suggesting that different NTs might be packaged into shared vesicles. We also examined whether the two splice variants of NGF, the short and long precursors, differ in their release characteristics. We found that neurons infected with viruses coding for either splice variant released NGF in a regulated way. Overall, our study supports the notion that all members of the NT family undergo activity-dependent regulated release from neurons, enabling them to act as "synaptotrophins" on electrically active neurons.

Animals↗
PubMed2004

Static mechanical hyperalgesia without dynamic tactile allodynia in patients with restless legs syndrome.

Pain sensitivity was assessed in 11 patients (age 60 +/- 10 years) with 'primary' restless leg syndrome (RLS) (disease duration 18 +/- 15 years) and 11 age- and gender-matched healthy control subjects. Stimulus-response functions for pricking pain were obtained with seven calibrated punctate mechanical stimulators activating Adelta-high threshold mechano-nociceptors. Stimuli at the foot were significantly more painful than at the hand in both patients and healthy control subjects both in the morning and evening. Generally, pin-prick pain ratings in RLS patients were significantly elevated, by a factor of 5.3 in the upper limb and by a factor of 6.4 in the lower limb indicating a significant generalized static hyperalgesia more pronounced in the lower limb. In contrast, pain to light touch (allodynia = dynamic mechanical hyperalgesia) as tested by a battery of three gentle tactile stimuli was never reported. Acute single-dose dopaminergic treatment with 100 mg levodopa + 25 mg benserazide, 90 min prior to the evening measurements, largely resolved patients' RLS symptoms, but had no effect on pin-prick pain. Static hyperalgesia to pin-prick, however, was significantly reversed (median reduction -74%) by long-term individually tailored dopaminergic treatment. Our study shows that patients with RLS exhibit a profound static mechanical hyperalgesia to pin-prick stimuli, but no dynamic mechanical hyperalgesia (allodynia). This type of hyperalgesia is probably mediated by central sensitization to Adelta-fibre high-threshold mechanoreceptor input, a hallmark sign of the hyperalgesia type of neuropathic pain. The reduction of hyperalgesia in RLS patients by long-term dopaminergic treatment suggests that the pathophysiology of RLS includes disturbed supraspinal pain modulation involving the basal ganglia and/or descending dopaminergic pathways.

Adult↗
PubMed2003

CSF hypocretin-1 levels in restless legs syndrome.

CSF hypocretin-1 levels at 6 PM did not significantly differ between patients with restless legs syndrome (RLS) and control subjects as measured by direct radioimmunoassay and after acid extraction. The authors did not observe significant differences between early onset and late onset RLS. Hypocretin-1 levels did not correlate with RLS severity or polysomnographic measures. These results contrast with previous findings reporting significantly increased CSF hypocretin-1 in the late evening and mostly in early onset RLS.

Adult↗
PubMed2003

[Pigmented form of orthochromatic leukodystrophy].

The pigmentary type of orthochromatic leukodystrophy (van Bogaert-Nyssen disease) is a hardly known neurological disorder usually with late onset that is very difficult to diagnose in vivo. Neuropathologically, the disorder features noninflammatory demyelination and the presence of pigmented macrophages and astrocytes that may contain iron. Clinically, van Bogaert-Nyssen disease can lead to death within a few years and is characterized by dementia, psychiatric abnormalities, epileptic seizures, spastic pareses, and occasionally extrapyramidal motor symptoms. This report presents a typical case and an overview of the literature. Furthermore, galactocerebroside could be documented in remaining macrophages and astrocytes by immunohistochemistry. This possibly indicates a dysfunction in sphingolipid breakdown and could relate the pigmented form of orthochromatic leukodystrophy to the genetically defined globoid cell leukodystrophy (Krabbe's disease). Thus, the rather heterogeneous pool of orthochromatic leukodystrophies could be further narrowed.

Adult↗
PubMed2002

Late-onset myoclonic epilepsy in Down's syndrome (LOMEDS).

The aim of this paper is to report a patient with late-onset myoclonic epilepsy in Down's syndrome (LOMEDS) as a differential diagnosis of adult-onset progressive myoclonic epilepsies. A 55-year-old male with Down's syndrome (DS) is described who developed progressively frequent myoclonus and generalized myoclonic-tonic seizures (GMTSs) at the age of 52. EEG recordings demonstrated background slowing and generalized polyspike-wave discharges occasionally associated with myoclonic jerks, leading to the classification of the primary generalized epileptic myoclonus. Descriptions of late-onset epilepsy in DS patients are rare. However, a review of the pertinent literature revealed at least two other cases of elderly DS patients developing progressive myoclonic epilepsy after the onset of dementia. We suggest that late-onset myoclonic epilepsy in Down's syndrome as characterized here should be considered in the differential diagnosis of adult-onset myoclonic epilepsies. LOMEDS apparently shares features with myoclonic epilepsy in Alzheimer's disease (AD) and Unverricht-Lundborg disease (ULD) caused by a mutation on chromosome 21. Since life expectation of DS patients has markedly increased, LOMEDS may be more frequent than currently acknowledged.

Alzheimer Disease↗
PubMed2001

Microglia and the early phase of immune surveillance in the axotomized facial motor nucleus: impaired microglial activation and lymphocyte recruitment but no effect on neuronal survival or axonal regeneration in macrophage-colony stimulating factor-deficient mice.

Activation of microglia is among the first cellular changes in the injured CNS. However, little is known about their specific contribution to secondary damage or repair processes in neighboring neurons and nonneuronal cells or to the immune surveillance of the damaged tissue. Animal models with defective microglial response such as osteopetrosis provide an approach to explore these effects. Osteopetrosis (op) is an autosomal recessive mutation with a complete deficiency of the macrophage-colony stimulating factor (MCSF; CSF-1), an important mitogen for brain microglia. In the current study we examined the effects of this MCSF deficiency on the microglial reaction and the overall cellular response to nerve injury in the mouse axotomized facial motor nucleus. In the brain, MCSF receptor immunoreactivity was found only on microglia and was strongly up-regulated following injury. MCSF deficiency led to a failure of microglia to show a normal increase in early activation markers (thrombospondin, MCSF receptor, alpha M beta 2- and alpha 5 beta 1-integrins), to spread on the surface of axotomized motoneurons, and to proliferate after injury. Early recruitment of CD3(+) T-lymphocytes to the facial nucleus 24 hours after injury was reduced by 60%. In contrast, the neuronal and astrocyte response was not affected. There was a normal increase in the neuropeptides calcitonin gene-related peptide and galanin, neuronal c-JUN, and NADPH-diaphorase and a decrease in choline acetyltransferase and acetylcholinesterase. Astrocyte glial fibrillary acidic protein immunoreactivity also showed a normal increase. There was a normal influx of macrophages and granulocytes into the injured facial nerve. Synaptic stripping, neuronal survival, and speed of axonal regeneration were also not affected. The current results show a strong, selective effect of MCSF on the early activation of microglia and, indirectly, on lymphocyte recruitment. This early phase of microglial activation appears not to be involved in the process of repair following peripheral nerve injury. However, it is important in the initiation of inflammatory changes in the brain and in the interaction with the immune system.

Animals↗
PubMed2001

[Parkinson disease. Directed use of modern therapy].

The approval of new antiparkinsonian drugs such as novel dopamine agonists or COMT-inhibitors during the last years has improved the therapeutic possibilities in Parkinson's disease. The choice of the different drugs depends on their particular efficiency, their adverse effect profile, the stage of the disease, the cardinal symptoms, age, and comorbidity. Therefore the physician is challenged to adjust the therapeutic management of each patient to the particular medical and social needs. This article discusses the present therapeutic strategies for the different stages of the disease detailing the profile, the main applications and the most important side effects of each drug.

Antiparkinson Agents↗
PubMed2001

Late-onset myoclonic epilepsy in Down's syndrome (LOMEDS).

The aim of this paper is to report a patient with late-onset myoclonic epilepsy in Down's syndrome (LOMEDS) as a differential diagnosis of adult-onset progressive myoclonic epilepsies. A 55-year-old male with Down's syndrome (DS) is described who developed progressively frequent myoclonus and generalized myoclonic-tonic seizures (GMTSs) at the age of 52. EEG recordings demonstrated background slowing and generalized polyspike-wave discharges occasionally associated with myoclonic jerks, leading to the classification of primary generalized epileptic myoclonus. Descriptions of late-onset epilepsy in DS patients are rare. However, a review of the pertinent literature revealed at least two other cases of elderly DS patients developing progressive myoclonic epilepsy after the onset of dementia. We suggest that late-onset myoclonic epilepsy in Down's syndrome as characterized here should be considered in the differential diagnosis of adult-onset myoclonic epilepsies. LOMEDS apparently shares features with myoclonic epilepsy in Alzheimer's disease (AD) and Unverricht-Lundborg disease (ULD) caused by a mutation on chromosome 21. Since life expectation of DS patients has markedly increased, LOMEDS may be more frequent than currently acknowledged.

Age Factors↗
PubMed2000

["Sleep attacks" in Parkinson patients. A side effect of nonergoline dopamine agonists or a class effect of dopamine agonists?].

Recently, sudden "sleep attacks" have been described in parkinsonian patients taking the nonergoline dopamine agonists pramipexole and ropinirole. Due to this possible side effect, patients must be instructed not to drive vehicles and to refrain from other activities carrying the risk of self-injury. However, the very existence of sleep attacks remains controversial in sleep medicine, since a gradual transition from wakefulness to sleep is normally observed. Accordingly, sudden onset of sleep, e.g., in narcolepsy or sleep apnea syndrome, is usually associated with excessive daytime sleepiness. Prevalence of sleep disorders and daytime sleepiness have been shown to be increased in Parkinson's disease. Nonergoline dopamine agonists are already known to induce somnolence. Currently, it is not predictable whether sleep attacks represent a sudden transition from wakefulness to sleep or result from an increased propensity to fall asleep, with patients perceiving a sudden onset. Possible pathophysiological mechanisms and legal implications of sleep attacks are discussed.

Accidents, Traffic↗
PubMed2000

Pramipexole in the treatment of advanced Parkinson's disease.

Pramipexole is a novel nonergoline dopamine agonist with a preference for the dopamine D3 receptor subtype. Its efficacy and safety in the treatment of advanced Parkinson's disease has been investigated in several clinical studies. This review provides a summary of the data currently available, particularly in reference to the recent results of the European clinical phase III study and the potential tremorlytic activity of pramipexole. Interim analysis of the open-label European clinical phase III study has provided evidence of long-term efficacy and safety of pramipexole. In another study pramipexole has been shown to be significantly superior to placebo with an improvement in tremor score by 48% (vs. 13% in the placebo group). In addition to its likely usefulness in the treatment of rest tremor in Parkinson's disease, data suggest that pramipexole is of interest due to its reported low frequency of cardiovascular and gastrointestinal side-effects. However, studies comparing pramipexole with other antiparkinsonian agents would be useful to further define its benefits in the treatment of tremor-dominant Parkinson's disease and to further document its favourable adverse event profile.

Benzothiazoles↗