Autosomal dominant striatal degeneration (ADSD): clinical description and mapping to 5q13-5q14.

OBJECTIVE: To describe the clinical and neuroradiologic features and chromosomal mapping of a novel autosomal dominant disease affecting the basal ganglia. METHODS: 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. RESULTS: 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. CONCLUSIONS: ADSD is an autosomal dominant basal ganglia disease mapping to chromosome 5q13.3-q14.1.

Pneumonia in acute stroke patients fed by nasogastric tube.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Neurosarcoidosis: clinical experience and diagnostic pitfalls.

OBJECTIVE: To describe a group of patients with neurosarcoidosis and to highlight diagnostic difficulties based on current diagnostic criteria. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Placing nasogastric tubes in stroke patients with dysphagia: efficiency and tolerability of the reflex placement.

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.

[Electric brain stimulation for epilepsy therapy]. / Elektrische Hirnstimulation in der Epilepsietherapie.

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").

[The megadolichobasilar artery--a clinical chameleon]. / Die dolichoectatische Basilaris. Ein klinisches Chamäleon.

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.

Hypnic headache - the first German cases including polysomnography.

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.

[Experience with tiagabine in the clinical practice; new insights as to the efficacy and safety profile]. / Erfahrung mit Tiagabin in der Praxis. Neue Aspekte zum Wirkungs- und Sicherheitsprofil.

Tiagabine is a relatively new anticonvulsive agent. Data concerning safety and efficacy come from randomised controlled trials whose relation to everyday clinical practice is poorly defined. We analysed retrospectively the data of 56 patients to whom tiagabine was routinely prescribed in a special clinic. Effect and adverse events were registered according to documentation of routine visits in the outpatient clinic. After a median of 89 weeks, 22 patients (39%) still received tiagabine. All of them noted a reduction in seizure frequency, and eight (14%) became seizure-free. Reasons for stopping the medication were: an increase in seizure frequency, lack of efficacy, tiagabine-associated non-convulsive status epilepticus and sudden and short episodes of mental chang. However, tiagabine seems to be an effective anticonvulsant in clinical practice but should remain in the hands of experienced prescribers until further clarification of possible risk factors for proconvulsive effects.

Clearance of melatonin and 6-sulfatoxymelatonin by hemodialysis in patients with end-stage renal disease.

Patients with end-stage renal disease (ESRD) suffer from a number of related disorders. These include endocrine abnormalities, sleep disturbances, and depression. Melatonin is involved in the synchronization of exogenous zeitgebers with the endogenous rhythms, and it has effects on various psychological factors. As the concentrations of melatonin and the effects of dialysis have only occasionally been investigated in ESRD, we performed a study involving 35 patients, measuring the serum concentrations of melatonin, and of its major metabolite 6-sulfatoxymelatonin (aMT6s), before and after hemodialysis. Serum samples taken during morning hours from a control group (n=11) with intact kidneys served as controls. Patients were dialyzed for approximately 4 hr between 07:00 and 13:00 hr (S1), between 13:00 and 20:00 hr (S2), or between 18:30 and 22:30 hr (S3). Mean melatonin concentrations before hemodialysis were highly elevated when compared with the controls (40.6 vs. 6.7 pg/mL; P<0.001). Although melatonin levels were decreased to 20.3 pg/mL after dialysis, they were still well above the control levels. Likewise, aMT6s concentrations before dialysis were highly elevated in ESRD patients before dialysis when compared with controls (39.5 vs. 2.0 pg/mL; P<0.001), and also decreased by dialysis to levels still well above control levels (25.3 pg/mL). Clearance efficacy was better for melatonin (48.9%) than for aMT6s (36.6%; P<0.05). In ESRD patients, a diurnal rhythm for melatonin was observed (S1, 45.1 pg/mL; S2, 31.5 pg/mL; S3, 48.7 pg/mL; P<0.05), indicating that the normal synthesis rhythm is maintained. None of the following secondary disorders were correlated with melatonin concentrations: insomnia, delayed sleep onset, night-time arousals, and restless-leg syndrome. The reason for this observation is probably the melatonin concentrations, which were so high that no sub-classification could be identified. It is concluded that in ESRD patients, hemodialysis is unable to decrease elevated levels of melatonin and aMT6s to normal values. It is speculated that some of the secondary disorders in ESRD are caused by supraphysiological concentrations of melatonin.

Simple method for placing nasogastric tubes in patients with dysphagia.

Patients who have had an acute stroke often have dysphagia and tube feeding becomes necessary. In these patients placing nasogastric tubes is often difficult, or even impossible. We describe a simple method for placing nasogastric tubes by inducing the swallowing reflex, which is independent of the patient's ability to co-operate. Among nine patients for whom the conventional methods had failed 20 placements were made, 19 of which were successful. Our approach is much less distressing for patients than conventional methods.

Disturbed benzodiazepine receptor function at the onset of temporal lobe epilepsy--lomanzenil-binding in de-novo TLE.

PURPOSE: Epileptogenic foci exhibit disturbed function at the level of the benzodiazepine receptor. The aim of our study was to investigate the incidence of focal reductions of temporal benzodiazepine receptor binding (BRB) as assessed by scintigraphy with 123I-iomazenil in patients with denovo temporal lobe epilepsy (TLE). METHODS: Forty adult patients (age: 34+/-12 years) with cryptogenic denovo TLE underwent scintigraphy with 123I-iomazenil. In all patients, symptomatic epilepsy was excluded by clinical investigation and MRI. The median duration of TLE was seven months, and the patients had a median of three documented seizures in their history of disease. BRB was quantified in four temporal regions covering the whole temporal lobe. Temporal asymmetry values (ASY) were compared with data determined in 13 age-matched controls yielding Z-scores for global and regional temporal BRB. RESULTS: A significant reduction of temporal BRB was found in 19 of the 40 patients (48 %), mainly in mesial temporal regions; temporal BRB asymmetries were also found in patients with a short history of seizures and low seizure frequency (< or = 1 year; n = 32, 13/32 (41 %)). Only in the entire cohort did the magnitude of temporal reduction of BRB correlate with the duration of TLE as well as with the number of previous partial seizures (r = 0.40 and r = 0.36; p < 0.03, respectively). CONCLUSIONS: Foci of decreased BRB can already be detected at the onset of TLE; their magnitude is related to ongoing epileptic activity.

Temporal hypometabolism at the onset of cryptogenic temporal lobe epilepsy.

Most patients with intractable temporal lobe epilepsy (TLE) exhibit temporal glucose hypometabolism. The reasons for the development of this abnormality are as yet unclear. The current notion is that an initial injury causes seizures, which in turn give rise to hypometabolism. The aim of this study was to assess whether temporal reductions in glucose metabolism in non-lesional TLE are the result of repeated seizures or whether hypometabolism represents an initial disturbance at the onset of disease. Glucose consumption was assessed with fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) in 62 patients with cryptogenic non-refractory TLE in different stages of disease. Twelve subjects without neurological illness served as controls. Patients with onset of epilepsy at least 3 years prior to the PET scan were defined as having chronic TLE. Using this criterion, the whole patient cohort included 27 patients with de novo TLE and 35 patients with chronic TLE. The groups were matched for age and sex. The appearance of high-resolution magnetic resonance images of the brain was unremarkable in all patients. In the total cohort, number, duration and frequency of seizures had a significant relation to the magnitude of hypometabolism. Temporal hypometabolism was exhibited by 26 of the 62 patients (42%), including 8 out of 27 (30%) with newly diagnosed TLE and 18 out of 35 (51%) with chronic TLE. The disturbances were more extensive and more severe in patients with chronic TLE. It is concluded that temporal hypometabolism may already be present at the onset of TLE, but is less frequent and less severe in newly diagnosed than in chronic TLE. The metabolic disturbance correlates with the number of seizures. These findings suggest that an initial dysfunction is present in a considerable number of patients and that hypometabolism is worsened by continuing epileptic activity.

Axonal polyneuropathy in obstructive sleep apnoea.

Chronic hypoxaemia in chronic obstructive pulmonary disease is a well known risk factor for polyneuropathy but the impact of intermittent hypoxaemia on peripheral nerve function has not been established so far. A case-control study was performed to evaluate the prevalence of polyneuropathy in obstructive sleep apnoea (OSA). Out of 24 patients with OSA, 17 (71%) had clinical signs of polyneuropathy versus seven (33%) out of 21 matched controls. The mean amplitude of the sural sensory nerve action potential was smaller in the OSA group than in the control group, indicating axonal nerve damage. The differences were significant and could not be attributed to other known risk factors for polyneuropathy. The severity of axonal damage in patients with OSA correlated with the percentage of the night time with an O(2) saturation below 90%. It is assumed that recurrent intermittent hypoxaemia in OSA is an independent risk factor for axonal damage of peripheral nerves.

Middle cerebral artery blood flow velocity, end-tidal pCO2 and blood pressure in patients with obstructive sleep apnea and in healthy subjects during continuous positive airway pressure breathing.

There is conflicting evidence in the literature as to the potential effect of continuous positive airway pressure (CPAP) on cerebral perfusion. Compromising cerebral perfusion could possibly outweigh the benefit of improved oxygenation. Patients with the obstructive sleep apnea syndrome (OSAS) have been claimed to have a higher cerebrovascular reactivity to changes in end-tidal pCO2. In this study, we investigated 23 patients with OSAS and 16 healthy young adults in the waking state. Both groups performed a series of 10 min of normal breathing, 20 min with 9 cmH2O nasal CPAP, and then 10 min of normal breathing while wearing a nasal CPAP mask. The following parameters were assessed: bilateral transcranial Doppler signal of the middle cerebral artery, systolic and diastolic blood pressure assessed manually, and cerebrovascular reactivity to changes in pCO2 during hyperventilation and rebreathing into an airbag. Continuous end-tidal pCO2 measurements were performed in 14 subjects. As compared with normal breathing middle cerebral artery blood flow velocity and pCO2 remained unchanged during CPAP. Systolic and diastolic blood pressure increased slightly by 1.2 mmHg (p = 0.015) and 1.1 mmHg (p = 0.007), respectively. Cerebrovascular reactivity did not differ in the two groups. Nasal CPAP of 9 cmH2O is a safe treatment with respect to the maintenance of cerebral blood flow. Our study gives further evidence for the autoregulation's capacity to maintain cerebral blood flow velocity constant during different levels of intrathoracic pressure and different cerebral perfusion pressures. We could not demonstrate any difference in cerebrovascular reactivity between patients with OSAS and healthy persons.