[Show abstract][Hide abstract] ABSTRACT: Autosomal-dominant striatal degeneration (ADSD) is an autosomal-dominant movement disorder affecting the striatal part of the basal ganglia. ADSD is characterized by bradykinesia, dysarthria, and muscle rigidity. These symptoms resemble idiopathic Parkinson disease, but tremor is not present. Using genetic linkage analysis, we have mapped the causative genetic defect to a 3.25 megabase candidate region on chromosome 5q13.3-q14.1. A maximum LOD score of 4.1 (Theta = 0) was obtained at marker D5S1962. Here we show that ADSD is caused by a complex frameshift mutation (c.94G>C+c.95delT) in the phosphodiesterase 8B (PDE8B) gene, which results in a loss of enzymatic phosphodiesterase activity. We found that PDE8B is highly expressed in the brain, especially in the putamen, which is affected by ADSD. PDE8B degrades cyclic AMP, a second messenger implied in dopamine signaling. Dopamine is one of the main neurotransmitters involved in movement control and is deficient in Parkinson disease. We believe that the functional analysis of PDE8B will help to further elucidate the pathomechanism of ADSD as well as contribute to a better understanding of movement disorders.
The American Journal of Human Genetics 01/2010; 86(1):83-7. DOI:10.1016/j.ajhg.2009.12.003 · 10.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obstructive sleep apnoea (OSA) is suggested to be associated with peripheral nerve damage. A case-control study was conducted to provide further support to this observation. In a longitudinal intervention study, it was examined whether treatment for OSA has a possible beneficial effect on peripheral nerve function.
Participants were 23 patients with OSA and 23 controls matched for age and body mass index (BMI), all without any known cause of peripheral nerve damage. The sensory nerve action potential (SNAP) amplitudes of both sural nerves were determined. After 6 months of treatment for OSA, treatment compliance was evaluated and nerve conduction studies were repeated.
Patients with OSA had significantly lower mean (standard deviation) sural SNAP amplitudes than controls (6.3 (3.5) v 11.2 (5.0), p < 0.001). Multivariate regression analysis including the variables age, BMI and Apnoea-Hypopnea Index (AHI) showed that both age (p < 0.01) and AHI (p < 0.05) were inversely related to the SNAP amplitude. On follow-up, the sural SNAP showed an increase of 2.6 mV on average (p < 0.001). Multivariate regression analysis including the variables age, BMI, AHI, pretreatment SNAP and treatment compliance identified only treatment compliance as being significantly related to the SNAP increase (p < or = 0.005).
OSA is an independent risk factor for axonal dysfunction of peripheral sensory nerves. Impaired neural function is at least partly reversible with treatment for sleep apnoea.
Journal of neurology, neurosurgery, and psychiatry 03/2007; 78(3):295-7. DOI:10.1136/jnnp.2006.102806 · 6.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nocturnal cardiac arrhythmia is a common clinical feature of obstructive sleep apnea syndrome. Pathologically relevant rhythm disturbances such as atrioventricular block or ventricular tachycardia are known to occur mainly in patients with a high apnea-hypopnea index and marked oxygen desaturation. We report on a patient with mild obstructive sleep apnea syndrome who nevertheless showed intermittent second-degree atrioventricular block during stages of rapid eye movement sleep-associated hypopneas. Cardiac arrhythmia was reversed with the initiation of nasal continuous positive airway pressure treatment. Based on this case report and taking into account known facts from the literature, the finding of intermittent second-degree atrioventricular block in our patient with mild obstructive sleep apnea syndrome supports careful evaluation of electrocardiogram recording acquired during polysomnography in all patients with suspected obstructive sleep apnea syndrome.
Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine 11/2006; 2(4):454-7. · 3.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Zusammenfassung Gutachterliche Fragestellungen bei Patienten mit einem Restless-Legs-Syndrom (RLS) nehmen stetig zu. Darum hat die “AG Motorik und Schlaf” der DGSM erstmals Empfehlungen zur Begutachtung und sozialmedizinischen Einschtzung des RLS erarbeitet. Im Folgenden werden die spezifischen Empfehlungen zur Beurteilung des RLS im Rahmen gutachterlicher Verfahren zusammengefasst (aus ). Diese Konsensusleitlinie soll eine Grundlage zur Vereinheitlichung und Qualittssicherung in der Begutachtung des RLS darstellen und nicht in individuelle Begutachtungen eingreifen.
Somnologie - Schlafforschung und Schlafmedizin 01/2006; 10(4):206-209.
[Show abstract][Hide abstract] ABSTRACT: Since sleep apnea (SA) and stroke have many shared risk factors an independent contribution of SA to the overall risk of stroke is not easily proven and has been questioned recently. To contribute to this controversy, we analysed the frequency of SA in groups of patients with first and recurring ischemic stroke. We prospectively studied 102 patients admitted to our stroke unit. The prevalence of vascular risk factors and a history of previous stroke were recorded. All patients received cardio-respiratory polygraphy during the first 72 hours after admission. CT and MRI scans were evaluated for the location of the acute stroke and the presence of older vascular lesions. Thirty-four women and 68 men with a mean age of 64.5 +/- 13.7 years were included in the study. Cerebral lesions attributable to a previous stroke were identified in 25 patients, of whom 19 reported to have suffered a stroke before. Patients with stroke recurrence had a higher mean apnea-hypopnea index (AHI) (26.6/h vs. 15.1/h, p<0.05) and more often presented with a sleep apnea syndrome (SA) defined by an AHI >or=10/h (80 vs. 52%, p < 0.05) than patients with first ever stroke. Logistic regression analysis including the variables "age", "gender", "cumulative risk factors", "AHI >or=10/h", and "diabetes" identified diabetes (Odd's ratio [OR]=4.5) and AHI >or=10/h (OR=3.5) as independent risk-factors for stroke recurrence. According to our results SA is an independent risk factor for stroke recurrence. We therefore advocate routine sleep-apnea screening in all patients having suffered an ischemic stroke.
Journal of Neurology 11/2005; 252(11):1394-8. DOI:10.1007/s00415-005-0888-7 · 3.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Regional abnormalities of cerebral glucose metabolism, as identified by 18-fluorodeoxyglucose positron emission tomography (FDG-PET) have prognostic value regarding the outcome of epilepsy surgery in patients with refractory partial epilepsy. The value of FDG-PET abnormalities in nonrefractory patients has not been investigated systematically. This study examines whether FDG-PET could be used for early identification of nonrefractory epilepsy in patients who will become pharmacoresistant later during the course of their disease.
We investigated interictal abnormalities of cerebral glucose metabolism by using FDG-PET in 125 consecutive patients with nonrefractory cryptogenic partial epilepsy and normal cranial magnetic resonance imaging (MRI), and we compared relative changes in seizure frequency in 90 patients after > or =2 years of follow-up.
Regional asymmetry of tracer distribution was seen in 43 of the 90 patients. Forty-one patients had regional glucose hypometabolism in the temporal and two patients in an extratemporal region. No difference between patients with and without a hypometabolic focus was found regarding seizure freedom after follow-up. This held true also for the subgroup of patients with epilepsy onset within 1 year before admission. Only patients with regional glucose metabolism showed an increase in seizure frequency. Multivariate analysis showed that only anticonvulsive treatment before index admission and the possibility of localizing the epileptogenic focus by using all available clinical and EEG data were independently associated with continuing seizures after a median follow-up period of 43 months.
Regional hypometabolism in FDG-PET is not significantly associated with a lower likelihood of successful anticonvulsant drug therapy in patients with nonrefractory partial epilepsy. Careful analysis of all routinely available clinical and neurophysiologic data has a much better predictive power to identify patients with medically refractory epilepsy early in the course of the disease. However, if PET data are available, they could help in identifying patients with a less benign course.
[Show abstract][Hide abstract] ABSTRACT: A case of subacute sclerosing panencephalitis in a 27-year-old man was serially evaluated with proton magnetic resonance spectroscopy. Metabolic abnormalities included decreased N-acetylaspartate and elevated choline and myo-inositol in a lesion visible on magnetic resonance imaging and in normal-appearing white matter. Lactate appeared increased within the lesion. Metabolic impairment was persistent after intrathecal interferon-alpha treatment. Spectroscopy pointing to ongoing inflammation, gliosis, and possible membrane turnover was more sensitive than imaging in detecting widespread pathology within the white matter.
Psychiatry Research 09/2005; 139(3):269-73. DOI:10.1016/j.pscychresns.2005.01.003 · 2.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sleep apnea syndrome (SAS) is a prominent clinical feature in acute stroke patients. Diagnosis is usually established by polysomnography or cardio-respiratory polygraphy (CRP). Both diagnostic procedures produce high costs, are dependent on the access to a specialized sleep laboratory, and are poorly tolerated by patients with acute stroke. In this study we therefore investigated whether capnography may work as a simple screening tool in this context. In addition to conventional CRP, 27 patients with acute stroke were studied with capnography provided by our standard monitoring system. The trend graphs of the end-tidal CO(2) values (EtCO(2)) were used to determine the capnography-based estimate of the apnea-hypopnea index (AHI(CO2)). Index events were scored when the EtCO(2) value dropped for > 50% of the previous baseline value. We found that the AHI(CO2) correlated significantly with the apnea-hypopnea index measured with conventional CRP (AHI(CRP)) (r = 0.94; p < 0.001). An AHI(CO2) > 5 turned out to be highly predictive of an AHI(CRP) > 10. According to our findings, routinely acquired capnography may provide a reliable estimate of the AHI(CRP). The equipment needed for this screening procedure is provided by the monitoring systems of most intensive care units and stroke units where stroke patients are regularly treated during the first days of their illness. Therefore, early diagnosis of SAS in these patients is made substantially easier.
Neurological Research 01/2005; 27(1):83-7. DOI:10.1179/016164105X18359 · 1.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aspiration pneumonia is the most important acute complication of stroke related dysphagia. Tube feeding is usually recommended as an effective and safe way to supply nutrition in dysphagic stroke patients.
To estimate the frequency of pneumonia in acute stroke patients fed by nasogastric tube, to determine risk factors for this complication, and to examine whether the occurrence of pneumonia is related to outcome.
Over an 18 month period a prospective study was done on 100 consecutive patients with acute stroke who were given tube feeding because of dysphagia. Intermediate outcomes were pneumonia and artificial ventilation. Functional outcome was assessed at three months. Logistic regression and multivariate regression analyses were used, respectively, to identify variables significantly associated with the occurrence of pneumonia and those related to a poor outcome.
Pneumonia was diagnosed in 44% of the tube fed patients. Most patients acquired pneumonia on the second or third day after stroke onset. Patients with pneumonia more often required endotracheal intubation and mechanical ventilation than those without pneumonia. Independent predictors for the occurrence of pneumonia were a decreased level of consciousness and severe facial palsy. The NIH stroke scale score on admission was the only independent predictor of a poor outcome.
Nasogastric tubes offer only limited protection against aspiration pneumonia in patients with dysphagia from acute stroke. Pneumonia occurs mainly in the first days of the illness and patients with decreased consciousness and a severe facial palsy are especially endangered.
[Show abstract][Hide abstract] ABSTRACT: To describe the clinical and neuroradiologic features and chromosomal mapping of a novel autosomal dominant disease affecting the basal ganglia.
The authors characterized a large family with autosomal dominant basal ganglia disease (ADSD) clinically and by MRI, MR spectroscopy (MRS), and SPECT. The authors performed a whole genome genetic linkage scan to map the underlying genetic defect.
The main clinical features of the disease are dysarthria and gait disturbance without any apparent reduction in life expectancy. MRI demonstrated a distinctive lesion pattern restricted mainly to the putamen and caudate nucleus. Genetic linkage analysis localized the causative genetic defect to a 3.25 megabase candidate region on chromosome 5q13.3-q14.1.
ADSD is an autosomal dominant basal ganglia disease mapping to chromosome 5q13.3-q14.1.
[Show abstract][Hide abstract] ABSTRACT: To describe a group of patients with neurosarcoidosis and to highlight diagnostic difficulties based on current diagnostic criteria.
The patient database of a general neurological department was searched for patients with established or suspected diagnosis of neurosarcoidosis. Twenty-four patients were identified with definite (n = 3), probable (n = 10) and possible neurosarcoidosis (n = 10). History and clinical, laboratory and imaging data of patients with definite and probable neurosarcoidosis were analyzed.
Cranial nerve symptoms were a dominant clinical feature, with the optic nerve being affected most frequently. Cerebrospinal fluid pleocytosis was found in more than half of the patients. Intrathecal IgG synthesis and oligoclonal bands were less frequent. There was a wide array of MRI lesions in both groups. Chest X-ray was false negative in 2 of 5 patients who also underwent a thoracic CT. Therapy with prednisolone was initiated in all patients. After a median of 36 months, 6 of 8 patients with follow-up data of >24 months were still in remission. Aggravation of symptoms required therapy escalation in 2 patients.
There is a wide range of clinical symptoms and test results in patients with "definite" or "probable" neurosarcoidosis. Because systemic involvement is a crucial diagnostic criterion, extensive medical work-up may be necessary. Prognosis under corticosteroid treatment may be better than previously thought.
European Neurology 03/2004; 51(2):84-8. DOI:10.1159/000076534 · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The highly variable clinical course of cervical artery dissections still poses a major challenge to the treating physician. This study was conducted (1) to describe the differences in clinical and angiographic presentation of patients with carotid and vertebral artery dissections (CAD, VAD), (2) to define the circumstances that are related to bilateral arterial dissections, and (3) to determine factors that predict a poor outcome. Retrospectively and by standardised interview, we studied 126 patients with cervical artery dissections. Preceding traumata, vascular risk factors, presenting local and ischemic symptoms, and patient-outcome were evaluated. Patients with CAD presented more often with a partial Horner's syndrome and had a higher prevalence of fibromuscular dysplasia than patients with VAD. Patients with VAD complained more often of neck pain, more frequently reported a preceding chiropractic manipulation and had a higher incidence of bilateral dissections than patients with CAD. Bilateral VAD was significantly related to a preceding chiropractic manipulation. Multivariate analysis showed that the variables stroke and arterial occlusion were the only independent factors associated with a poor outcome. This study emphasises the potential dangers of chiropractic manipulation of the cervical spine. Probably owing to the systematic use of forceful neck-rotation to both sides, this treatment was significantly associated with bilateral VAD. Patients with dissection-related cervical artery occlusion had a significantly increased risk of suffering a disabling stroke.
Journal of Neurology 11/2003; 250(10):1179-84. DOI:10.1007/s00415-003-0174-5 · 3.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Temporary dysphagia affects up to 50% of stroke patients in the acute stage of their illness and often necessitates tube feeding. In these patients, the placing of nasogastric tubes is often difficult or impossible. This study evaluated the efficiency and tolerability of a previously described new method for tube placing, which utilises the induction of the swallowing reflex and has therefore been called "reflex placement". In 14 of 16 patients in whom the conventional approach failed, the new method was successful. A comparison of the cardiovascular responses to both methods in another 12 patients revealed significantly smaller increases in heart rate and systolic blood pressure during application of the new method. We therefore suggest the use of reflex placement in patients who have suffered a stroke and need tube feeding due to dysphagia.
[Show abstract][Hide abstract] ABSTRACT: Attempts to control epileptic seizures by electrical brain stimulation have been performed for 50 years. Many different stimulation targets and methods have been investigated. Vagal nerve stimulation (VNS) is now approved for the treatment of refractory epilepsies by several governmental authorities in Europe and North America. However, it is mainly used as a palliative method when patients do not respond to medical treatment and epilepsy surgery is not possible. Numerous studies of the effect of deep brain stimulation (DBS) on epileptic seizures have been performed and almost invariably report remarkable success. However, a limited number of controlled studies failed to show a significant effect. Repetitive transcranial magnetic stimulation (rTMS) also was effective in open studies, and controlled studies are now being carried out. In addition, several uncontrolled reports describe successful treatment of refractory status epilepticus with electroconvulsive therapy (ECT). In summary, with the targets and stimulation parameters investigated so far, the effects of electrical brain stimulation on seizure frequency have been moderate at best. In the animal laboratory, we are now testing high-intensity, low-frequency stimulation of white matter tracts directly connected to the epileptogenic zone (e.g., fornix, corpus callosum) as a new methodology to increase the efficacy of DBS ("overdrive method").
Der Nervenarzt 09/2003; 74(8):664-76. · 0.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In patients with pontine hemorrhage (PH), an accurate prognostic assessment is critical for establishing a reasonable therapeutic approach.
The initial clinical symptoms and computed tomography (CT) features were analyzed with multivariate regression analysis in 39 consecutive patients with PH. PHs were classified into three types: (1) large paramedian, (2) basal or basotegmental and (3) lateral tegmental, and the hematomas' diameters were measured. The patients' outcome was evaluated.
Twenty-seven patients (69%) died and 12 (31%) survived for more than 1 year after PH. The symptom most predictive of death was coma on admission. The large paramedian type of PH predicted a poor prognosis, whereas the lateral tegmental type was associated with a favorable outcome. The transverse hematoma diameter was also related to outcome, with the threshold value found to be 20 mm.
We conclude that PH outcome can be estimated best by combining the CT parameters 'large paramedian PH' and 'transverse diameter >/=20 mm' with the clinical variable 'coma on admission'. Survival is unlikely if all 3 features are present, whereas survival may be expected if only 1 or none of these features is found.
[Show abstract][Hide abstract] ABSTRACT: Painful legs and moving toes (PLMT) is a rare syndrome which is characterised by involuntary movements of the toes and pain in the legs. We report on a mother and her daughter who both presented with involuntary movements of the toes similar to those seen in PLMT but without any associated pain. Neurological examination revealed intermittent 0.3 to 0.5-Hz flexion and extension of the toes and ankles of the right foot in the mother, and of both feet in the daughter. In both patients, the movements appeared during periods of rest that were uncorrelated with the time of day. Diagnostic work-up gave no evidence of radiculopathy or of focal neuropathy. Overnight polysomnography documented that movements of the toes and feet occurred only before sleep onset and during periods of nocturnal awakening or arousals. Because the movements observed in our patients were similar to those seen in patients with PLMT, we diagnosed an abortive form of this syndrome, which already has got the naming "painless legs and moving toes." The occurrence in a mother and her daughter may point to a hereditary component of this disorder.
Movement Disorders 06/2003; 18(6):718-22. DOI:10.1002/mds.10435 · 5.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report the first four German cases of hypnic headache according to the criteria suggested in the literature. Furthermore, we present the results of polysomnography in two theses cases with hypnic headache occurring during REM sleep. In one case, hypnic headache was also associated with periodic limb movements. Although mean nocturnal oxygen saturation was decreased in another patient, nightly oxygen inhalation did not result in an improvement of the headache.
[Show abstract][Hide abstract] ABSTRACT: The megadolichobasilar artery is a rare vascular disease, which usually becomes apparent either due to cerebral ischemia or due to compression of the brainstem or the cranial nerves, thereby leading to a large variety of neurological symptoms. We report on a patient who suffered a sudden right-sided deafness accompanied by vertigo and vomiting. Initially, an idiopathic sensorineural hearing loss was diagnosed and later on, after no improvement took place in spite of conservative therapy, a rupture of the round window membrane was suspected. Two weeks after the first symptoms had occurred the patient developed a hemiparesis on the left side.Radiology disclosed a dilated and partially thrombosed basilar artery as well as a paramedian pontine infarction. We therefore assumed that the patient's symptoms had been caused by thrombotic occlusion of the labyrinthine artery and several rami ad pontem. The article reviews the great variety of clinical symptoms caused by megadolichobasilar artery and discusses important therapeutic options.
Der Nervenarzt 03/2003; 74(2):172-4. · 0.79 Impact Factor