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Depression is a frequent and important complication after stroke. The occurrence of a post-stroke-depression (PSD) has a significant impact on the functional and cognitive deficit, on mortality and on quality of life after stroke. In contrast to the clinical importance, PSD is often ignored in routine management of stroke patients and remains often untreated if diagnosed. The diagnostic uncertainty is aggravated by the lack of appropriate diagnostic criteria for PSD in the International Classification of Diseases (ICD-10) used in Germany. For the first time, we present an algorithm, which allows for a standardized examination of stroke patients on the presence of PSD. All stroke patients should be examined initially by a short and simple screening tool and are subjected to more extensive procedures only if PSD is assumed based on the screening result. Furthermore potentials and limitations to convert the diagnosis of PSD into a diagnostic related group (DRG) that is used to calculate the hospital's reimbursement are highlighted. Finally pharmacological treatment options for PSD are discussed.

A G309D mutation in the PINK1 gene in a consanguineous Spanish kindred with seven siblings, three of whom are clinically affected, has recently been shown to be a cause of the PARK6 form of autosomal-recessive Parkinson's syndrome. In this family, we studied pre- and postsynaptic dopaminergic function using 123I-FP-CIT- and 123I-iodobenzamide-SPECT to determine binding to the presynaptic dopamine transporter (DAT) and postsynaptic D2 receptors respectively. All three PARK6 patients showed reduced striatal DAT binding with posterior preponderance similar to sporadic idiopathic PD, but only one patient showed significant striatal asymmetry. In two of the siblings, DAT binding was markedly increased. IBZM-SPECT was normal in both patients and sibs. Our findings indicate that 123I-FP-CIT-SPECT shows similar DAT binding in PARK6 patients compared to idiopathic Parkinson's disease. The increased DAT binding in heterozygous PARK6 carriers may be a new very early preclinical finding, but its significance is still unclear.

OBJECTIVES—Botulinum toxin injections have become a first line therapeutic approach in cervical dystonia. Nevertheless, published dosing schedules, responder rates, and frequency of adverse events vary widely. The present prospective multicentre placebo controlled double blind dose ranging study was performed in a homogenous group of previously untreated patients with rotational torticollis to obtain objective data on dose-response relations. METHODS—Seventy five patients were randomly assigned to receive treatment with placebo or total doses of 250, 500, and 1000 Dysport® units divided between one splenius capitis (0, 175, 350, 700 units) and the contralateral sternocleidomastoid (0, 75, 150, 300 units) muscle. Assessments were obtained at baseline and weeks 2, 4,and 8 after treatment and comprised a modified Tsui scale, a four point pain scale, a checklist of adverse events, global assessment of improvement, and a global rating taking into account efficacy and adverse events. At week 8 the need for retreatment was assessed and then the code was unblinded. For those still responding, there was an open follow up until retreatment to assess the duration of effect. RESULTS—seventy nine per cent reported subjective improvement at one or more follow up visits. Decreases in the modified Tsui score were significant at week 4 for the 500 and 1000 unit groups versus placebo (p

HISTORY AND ADMISSION FINDINGS Over the period of one year three long-distance airline passengers (aged 21, 63, and 64 years) were admitted to our department because of a first-time acute neurological deficit having occurred during their long-distance flights. INVESTIGATIONS In all three cases acute stroke MRI showed embolic cerebral ischemia, and transesophageal echocardiography revealed a persistent foramen ovale (PFO). Venous duplex and compression ultrasonography of the legs showed no signs of thrombosis. Extra- and transcranial Doppler, Holter ECG recording, routine blood analysis and additional tests for thrombophilia (incl. lupus anticoagulans, APC resistance, protein C, S, and AT III) revealed no signs of cardiovascular disease or other stroke causes. Only in case 3 the prothrombin gene G 20210A was found. DIAGNOSIS, TREATMENT AND COURSE Ischemic stroke due to paradoxical embolism through a PFO was diagnosed in all three patients. One patient recovered fully within 2 days, one was discharged with a persistent motor deficit and the third patient died subsequently as a result of multiple cerebral infarctions accompanied by massive pulmonary embolism. CONCLUSION These three cases illustrate that paradoxical embolic stroke is a possible severe complication of long-distance air travel in passengers with a PFO and this should be taken into account when deciding upon individual risk-adjusted prophylactic measures.

Depression is a frequent and important complication after stroke. The occurrence of a post-stroke-depression (PSD) has a significant impact on the functional and cognitive deficit, on mortality and on quality of life after stroke. In contrast to the clinical importance, PSD is often ignored in routine management of stroke patients and remains often untreated if diagnosed. The diagnostic uncertainty is aggravated by the lack of appropriate diagnostic criteria for PSD in the International Classification of Diseases (ICD-10) used in Germany. For the first time, we present an algorithm, which allows for a standardized examination of stroke patients on the presence of PSD. All stroke patients should be examined initially by a short and simple screening tool and are subjected to more extensive procedures only if PSD is assumed based on the screening result. Furthermore potentials and limitations to convert the diagnosis of PSD into a diagnostic related group (DRG) that is used to calculate the hospital's reimbursement are highlighted. Finally pharmacological treatment options for PSD are discussed.

Objectives: Mortality is high and functional outcome poor in mechanically ventilated stroke patients. In addition, age >65 years is an independent predictor of death at 2 months among these patients. Our objective was to determine survival rates, functional outcome, and quality of life (QoL) in stroke patients older than 65 years requiring mechanical ventilation. Methods: A prospective cohort study with an additional cross-sectional survey in 65 patients aged 65 years and older (mean age (SD): 75.6 (6.0) years) with ischaemic or haemorrhagic stroke who underwent mechanical ventilation. Main outcome measures were survival rate at 6 months, and Barthel Index (BI), modified Rankin Scale, and QoL at 15.8 (SD 8.0) months. Results: Survival rate at 6 months was 40%. Elective intubation (odds ratio (OR) 13.6; p = 0.002) was the only independent positive predictor for survival, while age >77.5 years (OR 0.1; p = 0.004) and white blood count >10/nl at admission (OR 0.31; p = 0.032) were independent negative predictors for survival at 6 months. At the time of the cross-sectional survey, BI was >70 in five out of 22 patients, 35–70 in three and

Patients with Parkinson's disease (PD) frequently suffer from cardiovascular dysfunction, which may be enhanced to various extents by different antiparkinsonian drugs.We analysed electrocardiogram (ECG) abnormalities, cardiovascular reflexes (CVR) and orthostatic hypotension (OH) in 148 patients with idiopathic PD assigned to five different combination therapies of levodopa (LD) plus either bromocriptine (BRO), ropinirole (ROP), selegiline (SEL), anticholinergic (ACH) or amantadine (AMA) or to LD monotherapy before and after a 1-week washout of the add-on drug. Patients were matched for age and disease severity (Hoehn and Yahr stage 2-3). Rater-blinded cardiovascular testing was performed at baseline, and following a 1-week washout period of the add-on drugs.We found that the incidence of cardiovascular dysfunction was generally higher in patients receiving a combination therapy compared with patients on LD monotherapy. ECG abnormalities were found in 40-52% of patients in combination therapy, but in only 20% of the patients receiving LD monotherapy. After discontinuation of BRO and SEL, there were significant improvements in ECG, OH and CVR. After washout of ACH and AMA, a significant improvement was found only in the CVR score. AMA and ROP were the add-on drugs with the least adverse cardiovascular effects.We conclude that pre-existing cardiovascular autonomic dysfunction should be investigated and taken into account when deciding which combination therapy to choose in the treatment of parkinsonian patients.

Over the period of one year three long-distance airline passengers (aged 21, 63, and 64 years) were admitted to our department because of a first-time acute neurological deficit having occurred during their long-distance flights.In all three cases acute stroke MRI showed embolic cerebral ischemia, and transesophageal echocardiography revealed a persistent foramen ovale (PFO). Venous duplex and compression ultrasonography of the legs showed no signs of thrombosis. Extra- and transcranial Doppler, Holter ECG recording, routine blood analysis and additional tests for thrombophilia (incl. lupus anticoagulans, APC resistance, protein C, S, and AT III) revealed no signs of cardiovascular disease or other stroke causes. Only in case 3 the prothrombin gene G 20210A was found.Ischemic stroke due to paradoxical embolism through a PFO was diagnosed in all three patients. One patient recovered fully within 2 days, one was discharged with a persistent motor deficit and the third patient died subsequently as a result of multiple cerebral infarctions accompanied by massive pulmonary embolism.These three cases illustrate that paradoxical embolic stroke is a possible severe complication of long-distance air travel in passengers with a PFO and this should be taken into account when deciding upon individual risk-adjusted prophylactic measures.

Data from 616 patients suffering from idiopathic cervical dystonia were analyzed to determine the efficacy and safety of treatment with botulinum neurotoxin type A (BoNT/A). Since the specific purpose of this study was to determine the long-term effects of this treatment, the analysis focused specifically on the patients (n = 303) having received six or more injections. Statistical analysis of a standardized documentation showed sustained significant benefit as measured by a disease severity score independent of the type of cervical dystonia. Furthermore, pronounced individual differences were found in response to this treatment although initial clinical scores and doses of BoNT/A were similar. There was no indication of previously unknown adverse events, the only risk being the development of serum antibodies against the toxin. As in previous studies on short-term effects of BoNT/A treatment, the most frequent adverse event was dysphagia, which occurred on average 9.7 days after injection and lasted on average 3.5 weeks. While secondary nonresponse was seen in approx. 5% of patients, antibody tests revealed neutralizing serum antibodies in only 2%. On the basis of the present data, therapy of cervical dystonia with BoNT/A seems to be safe and yields good stable results even after 5 years of treatment.

During forearm tracking of a sinusoidally moving target matching of proprioceptive and visual feedback was altered by introducing different visual delays. In five normal subjects seven target frequencies were tested ranging from 0.3 to 1.5 Hz. For each target frequency nine different delays were used ranging from 0 to 120% of the cycle duration with target frequency and delay being varied randomly. Tracking error revealed a cyclic behaviour with an increase up to delays of about 50% of the target cycle duration and an improvement for delays larger than 50%. Modulation of response frequency was less pronounced compared with tracking error variation but also was dependent on relative phase. The response frequency matched the target frequency at delays of 0 and 100% of cycle duration and was slightly lower than the target frequency with relative delays of about 50%. The introduction of a visual delay during sinusoidal forearm tracking leads to a spatial in addition to the temporal mismatch between proprioception and vision. The temporal and the spatial incompatibility influence the tracking performance differentially.

Botulinum toxins, exotoxins of Clostridium botulinum, are the most toxic naturally occurring substances known to man. For more than a century they are known to be the cause of botulism, a nowadays rare intoxication with spoiled food that leads to generalized flaccid weakness of striated muscle including pharyngeal and respiratory musculature. The toxins act primarily at peripheral cholinergic motor nerve endings by blocking the release of the neurotransmitter acetylcholine. As a consequence, action potentials in the motor nerve can no longer be transmitted to the muscle. This lack in transmission, clinically appearing as weakness, may disable or actually critically endanger affected patients. However, in certain neurological diseases characterized by an abnormal increase in muscle tone or activity, for example dystonia or spasticity, a reduction in signal transmission may actually be beneficial. Around 1980 local injections of minute amounts (in the order of 0.5 ng) of Botulinum toxin type A were first successfully used in a neurological disorder named blepharospasm which is characterized by an involuntary squinting of the eyes. Since then Botulinum toxin has developed rapidly from a frightful poison to a safe therapeutic agent with a remarkable beneficial impact on the quality of life of many thousands of patients worldwide. This review tries to outline in brief the characteristics of Botulinum toxins, their mechanism of action and the various indications for clinical use as a therapeutic agent.