Semantic memory and depressive symptoms in patients with subjective cognitive decline, mild cognitive impairment, and Alzheimer's disease.

BACKGROUND: Semantic memory may be impaired in clinically recognized states of cognitive impairment. We investigated the relationship between semantic memory and depressive symptoms (DS) in patients with cognitive impairment. METHODS: 323 cognitively healthy controls and 848 patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia were included. Semantic knowledge for famous faces, world capitals, and word vocabulary was investigated. RESULTS: Compared to healthy controls, we found a statistically significant difference of semantic knowledge in the MCI groups and the AD group, respectively. Results of the SCD group were mixed. However, two of the three semantic memory measures (world capitals and word vocabulary) showed a significant association with DS. CONCLUSIONS: We found a difference in semantic memory performance in MCI and AD as well as an association with DS. Results suggest that the difference in semantic memory is due to a storage loss rather than to a retrieval problem.

Limb-kinetic apraxia affects activities of daily living in Parkinson's disease: a multi-center study.

BACKGROUND AND PURPOSE: Impaired dexterity (fine hand movements) is often present in Parkinson's disease (PD), even at early to moderate disease stages. It has a detrimental impact on activities of daily living (ADL) such as buttoning, contributing to reduced quality of life. Limb-kinetic apraxia, a loss of the ability to make precise, independent but coordinated finger and hand movements, may contribute to impaired dexterity even more than bradykinesia per se. However, the impact of limb-kinetic apraxia on ADL remains controversial. Our aim was to identify the strongest predictor of buttoning and unbuttoning in PD. It was hypothesized that coin rotation (a surrogate of limb-kinetic apraxia) represents the most important determinant. METHODS: Sixty-four right-handed, early to moderate PD patients were recruited from three movement disorder centers (Hoehn andYahr stages 1-3). Buttoning, unbuttoning and coin rotation (right and left hand) represented the target tasks. Motor impairment was assessed according to the Unified Parkinson's Disease Rating Scale. RESULTS: Multiple linear regression analysis showed that coin rotation with the right hand was the only significant predictor of buttoning (P < 0.001) and unbuttoning (P = 0.002). Notably, measures of bradykinesia or overall motor impairment did not represent significant predictors. CONCLUSIONS: Constituting the novel key finding, limb-kinetic apraxia seems to be particularly relevant for ADL requiring dexterity skills in PD, even at early to moderate disease stages. Our results prompt research into the pathophysiological background and therapeutic options to treat limb-kinetic apraxia. The simple coin rotation test provides valuable information about ADL-related dexterity skills.

Endovascular stroke therapy in Austria: a nationwide 1-year experience.

BACKGROUND AND PURPOSE: Based on a tight network of stroke units (SUs) and interventional centres, endovascular treatment of acute major intracranial vessel occlusion has been widely implemented in Austria. Documentation of all patients in the nationwide SU registry has thereby become mandatory. METHODS: Demographic, clinical and interventional characteristics of patients who underwent endovascular treatment for acute ischaemic stroke in 11 Austrian interventional centres between 1 October 2013 and 30 September 2014 were analysed. RESULTS: In total, 301 patients (50.5% women; median age 70.5 years; median National Institutes of Health Stroke Scale score 17) were identified.193 patients (64.1%) additionally received intravenous thrombolysis. The most frequent vessel occlusion sites were the M1 segment of the middle cerebral artery (n = 161, 53.5%), the intracranial internal carotid artery (n = 60, 19.9%) and the basilar artery (n = 40, 13.3%). Stent retrievers were used in 235 patients (78.1%) and adequate reperfusion (modified Thrombolysis in Cerebral Infarction scores 2b and 3, median onset to reperfusion time 254 min) was achieved in 242 patients (81.4%). Symptomatic intracranial haemorrhage occurred in 7%. 43.8% of patients (n = 132) had good functional outcome (modified Rankin Scale score 0-2) and the mortality rate was 20.9% (n = 63) after 3 months. Compared to the anterior circulation, vertebrobasilar stroke patients had higher mortality. Patients with secondary hospital transportation had better outcomes after 3 months than in-house treated patients. CONCLUSION: Our results document nationwide favourable outcome and safety rates of endovascular stroke treatment comparable to recent randomized trials. The ability to provide such data and the need to further optimize such an approach also underscore the contribution of respective registries.

The impact of depressive symptoms on health-related quality of life in patients with subjective cognitive decline, mild cognitive impairment, and Alzheimer's disease.

BACKGROUND: Health-related quality of life (HRQOL) is an important issue in the context of dementia care. The purpose of this study was to investigate the association between HRQOL and depressive symptoms in patients with subjective cognitive decline (SCD) and subtypes of mild cognitive impairment (MCI) and Alzheimer´s disease (AD). METHODS: In this cross-sectional, observational study, a control group and four experimental groups (SCD, non-amnestic MCI, amnesticMCI, AD) were compared. Neuropsychological measurers (NTBV) and psychological questionnaires were used for data collection. RESULTS: The control group scored higher than patients with SCD, naMCI, aMCI, or AD for the Mental Health Component Score (MHCS) of the Short Form of the Health Survey (SF-36). The Physical Health Component Score (PHCS) of the SF-36 differed only between some groups. Furthermore, cognitive variables were more strongly associated with the physical aspects of HRQOL, whereas depressive symptoms were more strongly related with the mental aspects of HRQOL. CONCLUSIONS: HRQOL and depressive symptoms are closely related in patients with cognitive impairments. Therefore, it is of great importance to assess patients with subjective impairment carefully in terms of depressive symptoms.

Facial emotion recognition in patients with subjective cognitive decline and mild cognitive impairment.

BACKGROUND: Deficits in facial emotion recognition (FER) have been shown to substantially impair several aspects in everyday life of affected individuals (e.g. social functioning). Presently, we aim at assessing differences in emotion recognition performance in three patient groups suffering from mild forms of cognitive impairment compared to healthy controls. METHODS: Performance on a concise emotion recognition test battery (VERT-K) of 68 patients with subjective cognitive decline (SCD), 44 non-amnestic (non-aMCI), and 25 amnestic patients (aMCI) with mild cognitive impairment (MCI) was compared with an age-equivalent sample of 138 healthy controls all of which were recruited within the framework of the Vienna Conversion to Dementia Study. Additionally, patients and controls underwent individual assessment using a comprehensive neuropsychological test battery examining attention, executive functioning, language, and memory (NTBV), the Beck Depression Inventory (BDI), and a measure of premorbid IQ (WST). RESULTS: Type of diagnosis showed a significant effect on emotion recognition performance, indicating progressively deteriorating results as severity of diagnosis increased. Between-groups effect sizes were substantial, showing non-trivial effects in all comparisons (Cohen's ds from -0.30 to -0.83) except for SCD versus controls. Moreover, emotion recognition performance was higher in women and positively associated with premorbid IQ. CONCLUSIONS: Our findings indicate substantial effects of progressive neurological damage on emotion recognition in patients. Importantly, emotion recognition deficits were observable in non-amnestic patients as well, thus conceivably suggesting associations between decreased recognition performance and global cognitive decline. Premorbid IQ appears to act as protective factor yielding lesser deficits in patients showing higher IQs.

Facial emotion recognition and its relationship to cognition and depressive symptoms in patients with Parkinson's disease.

BACKGROUND: Impairments in facial emotion recognition (FER) have been detected in patients with Parkinson disease (PD). Presently, we aim at assessing differences in emotion recognition performance in PD patient groups with and without mild forms of cognitive impairment (MCI) compared to healthy controls. METHODS: Performance on a concise emotion recognition test battery (VERT-K) of three groups of 97 PD patients was compared with an age-equivalent sample of 168 healthy controls. Patients were categorized into groups according to two well-established classifications of MCI according to Petersen's (cognitively intact vs. amnestic MCI, aMCI, vs. non-amnestic MCI, non-aMCI) and Litvan's (cognitively intact vs. single-domain MCI, sMCI, vs. multi-domain MCI, mMCI) criteria. Patients and controls underwent individual assessments using a comprehensive neuropsychological test battery examining attention, executive functioning, language, and memory (Neuropsychological Test Battery Vienna, NTBV), the Beck Depression Inventory, and a measure of premorbid IQ (WST). RESULTS: Cognitively intact PD patients and patients with MCI in PD (PD-MCI) showed significantly worse emotion recognition performance when compared to healthy controls. Between-groups effect sizes were substantial, showing non-trivial effects in all comparisons (Cohen's ds from 0.31 to 1.22). Moreover, emotion recognition performance was higher in women, positively associated with premorbid IQ and negatively associated with age. Depressive symptoms were not related to FER. CONCLUSIONS: The present investigation yields further evidence for impaired FER in PD. Interestingly, our data suggest FER deficits even in cognitively intact PD patients indicating FER dysfunction prior to the development of overt cognitive dysfunction. Age showed a negative association whereas IQ showed a positive association with FER.

Differential functional benefits of ultra highfield MR systems within the language network.

Several investigations have shown limitations of fMRI reliability with the current standard field strengths. Improvement is expected from ultra highfield systems but studies on possible benefits for cognitive networks are lacking. Here we provide an initial investigation on a prominent and clinically highly-relevant cognitive function: language processing in individual brains. 26 patients evaluated for presurgical language localization were investigated with a standardized overt language fMRI paradigm on both 3T and 7T MR scanners. During data acquisition and analysis we made particular efforts to minimize effects not related to static magnetic field strength differences. Six measures relevant for functional activation showed a large dissociation between essential language network nodes: although in Wernicke's area 5/6 measures indicated a benefit of ultra highfield, in Broca's area no comparison was significant. The most important reason for this discrepancy was identified as being an increase in susceptibility-related artifacts in inferior frontal brain areas at ultra high field. We conclude that functional UHF benefits are evident, however these depend crucially on the brain region investigated and the ability to control local artifacts.

Subjective memory complaints, depressive symptoms and cognition in Parkinson's disease patients.

BACKGROUND AND PURPOSE: The goal of this study was to establish the prevalence of subjective memory complaints (SMCs) and depressive symptoms (DS)s and their relation to cognitive functioning in patients with Parkinson's disease (PD). METHODS: In all, 248 controls and 104 PD patients were included in the study. The PD group was subdivided into three PD subtypes with mild cognitive impairment (MCI) according to the Petersen criteria and three PD subtypes with MCI according to the Litvan criteria. RESULTS: Substantial SMCs were reported by 7.7% of controls and 16.3% of the PD patients (P < 0.001). A clinically relevant degree of DSs was evident in 16.6% of controls compared with 40.4% in the PD group (P < 0.001). An analysis of variance revealed a statistically significant difference for SMCs across all Petersen groups as well across all Litvan groups. Two-factor analyses of variance with the factors cognitive status (MCI subtype) and depressive state (depressed versus not depressed) and SMCs as dependent variable revealed significant results. CONCLUSIONS: Approximately 15% of PD patients seeking help in a movement disorder clinic report significant SMCs, with an increasing degree from cognitively healthy PD to PD-MCI. Significant DSs increase SMCs across all cognitive status groups.

Subjective memory complaints, depressive symptoms and cognition in patients attending a memory outpatient clinic.

BACKGROUND: The goals of this study were to establish prevalence of subjective memory complaints (SMC) and depressive symptoms (DS) and their relation to cognitive functioning and cognitive status in an outpatient memory clinic cohort. METHODS: Two hundred forty-eight cognitively healthy controls and 581 consecutive patients with cognitive complaints who fulfilled the inclusion criteria were included in the study. RESULTS: A statistically significant difference (p < 0.001) between control group and patient group regarding mean SMC was detected. 7.7% of controls reported a considerable degree of SMC, whereas 35.8% of patients reported considerable SMC. Additionally, a statistically significant difference (p < 0.001) between controls and patient group regarding Beck depression score was detected. 16.6% of controls showed a clinical relevant degree of DS, whereas 48.5% of patients showed DS. An analysis of variance revealed a statistically significant difference across all four groups (control group, SCI group, naMCI group, aMCI group) (p < 0.001). Whereas 8% of controls reported a considerable degree of SMC, 34% of the SCI group, 31% of the naMCI group, and 54% of the aMCI group reported considerable SMC. A two-factor analysis of variance with the factors cognitive status (controls, SCI group, naMCI group, aMCI group) and depressive status (depressed vs. not depressed) and SMC as dependent variable revealed that both factors were significant (p < 0.001), whereas the interaction was not (p = 0.820). CONCLUSIONS: A large proportion of patients seeking help in a memory outpatient clinic report considerable SMC, with an increasing degree from cognitively healthy elderly to aMCI. Depressive status increases SMC consistently across groups with different cognitive status.

The effect of early prednisolone treatment on the generalization rate in ocular myasthenia gravis.

BACKGROUND AND PURPOSE: Several small retrospective studies have observed that patients with a purely ocular manifestation of myasthenia gravis (MG) are significantly less likely to convert to a generalized disease when treated early on with corticosteroids. However, given the limited number of reported patients in the literature these findings still remain controversial. METHODS: In order to increase the number of published cases, we performed a retrospective analysis on 44 patients with newly diagnosed ocular MG who were subsequently either treated with corticosteroids or received no immunosuppressive therapy at all. The generalization rate was assessed at the end of a 2-year follow-up period. RESULTS: Whereas none of 17 treated patients generalized, 11 of 27 (41%) untreated patients developed generalized symptoms. The difference between the groups was significant (P=0.003). CONCLUSIONS: Our results agree well with previous studies on this issue. Taken together, published data indicate risk ratios for generalization of below 0.32 under corticosteroid treatment in comparison to untreated patients.

Long-term efficacy and respective potencies of botulinum toxin A and B: a randomized, double-blind study.

BACKGROUND: Mouse units (mU) are used for quantification of the biological activity of botulinum A and B toxin preparations. However, in human tissue, mU values between preparations are not equivalent and lack of clarity concerning efficacy and safety remains with regard to their respective potencies, duration of drug effect and diffusion qualities. OBJECTIVES: To compare short-term and long-term effects of Botox(®) (BOT; Allergan Inc., Irvine, CA, U.S.A.) and Neurobloc(®)/Myobloc(®) (NBC; Solstice Neurosciences Inc., Malvern, PA, U.S.A.) in different doses and dilutions in a human skin model. METHODS: In this prospective randomized double-blind study, 18 healthy volunteers (eight women and 10 men; mean ± SD age 28·4 ± 5·7 years) were injected intradermally with pure saline, BOT and NBC at 10 points in the abdomen in random order, using the BOT/NBC conversion ratio 1 : 75 and different dilution schemes. For an objective outcome, the ninhydrin sweat test was used to compare the anhidrotic areas (action halos). Ten measurements were taken during a time period of 54 weeks. RESULTS: Both preparations showed a peak effect at week 3, with significantly larger anhidrotic areas for NBC. Thereafter, however, the rate of decline was lower in BOT and after week 24, mean BOT areas were larger. The effect of dilution was higher in NBC and the mean dose equivalence conversion ratio (BOT/NBC) was 1 : 29 (area under the curve). Gender effects were seen in both products, with smaller action halos in women. CONCLUSIONS: These results have important implications in clinical routine, especially for autonomic indications.

Disruption of nigrostriatal and cerebellothalamic pathways in dopamine responsive Holmes' tremor.

Holmes' tremor is an unusual combination of rest, postural and kinetic tremor of the extremities. Medical treatment of this condition still remains unsatisfactory. The case of a 20-year-old female patient is reported who developed right-sided Holmes' tremor 9 months after a left-sided, cavernoma induced midbrain/pontine haemorrhage at the age of 16 years. Beta-CIT single photon emission computed tomography revealed abolished dopamine transporter activity in the left basal ganglia and striatum, in accordance with missing ipsilateral tegmento-frontal connectivity (medial forebrain bundle), demonstrated by diffusion tensor MRI. Tractography showed reduced fibre connectivity of the superior and middle cerebellar peduncles on the lesioned side. Administration of pramipexole and L-DOPA led to a clinically significant reduction in tremor severity. In conclusion, our results support the notion that Holmes' tremor was a result of diminished striatal dopaminergic input in our patient.

[What roll does the sense of coherence in coping with Morbus Parkinson play?]. / Welche Rolle spielt das Kohärenzgefühl in der Krankheitsverarbeitung bei Morbus Parkinson?

PURPOSE OF THE STUDY: In this study the relevance of sense of coherence (SOC) for coping with an illness was examined in subjects with Parkinson's disease. According to Antonovsky's model (1997) the sense of coherence is an important resource when it comes to dealing with stressors. To take into consideration the integrated view of Parkinson patients, severity of the illness (UPDRS) was determined by the neurologist and tendency toward depression was recorded. METHOD: 51 patients with PD (mean age: 67.7; 43.1% female; 56.9% male) and 59 volunteers without any neurological illness (mean age: 65.7; 54.2% female; 45.8% male) took part in this study. The sample was recruited from the Neurological Department of the Medical University of Vienna. This quasi-experimental sample was assessed with standardized self-assessment questionnaires: FKV-LIS-SE, SOC-Scale and GDS. Correlations, t-tests, U-tests, multivariate analyses of variance and linear regressions were used for calculation. RESULTS: Persons with PD were characterized by lower SOC (p<.01) and higher scores on depression (p<.01), compared to persons of the control group. Parkinson patients tend to use depressive and minimizing coping strategies (p<.01). In addition the study indicates an influence of SOC and tendency toward depression on coping (R(2)=0.43). Sense of coherence and coping strategies are independent of severity of illness, but there is a significant association between the duration of illness and active-problem focused coping. CONCLUSION: In general, sense of coherence correlates only with psychological variables, and not with physical variables. Results indicate the importance of SOC on effective coping. Therefore strengthening of SOC is important, especially in context with chronic neurological illness. Individual orientated analysis of resources should be implemented in every counselling interview, so that possibilities for activities of daily living and leisure can be developed.

Loss of normal circadian profile of urine excretion in idiopathic restless legs syndrome.

BACKGROUND: This study was performed to elucidate preliminary observations of excessive nighttime urine excretion in idiopathic restless legs syndrome (iRLS). METHODS: Seventeen patients, with normal serum creatinine, blood urea nitrogen, and urate, and 11 healthy controls were examined. We measured excretory renal function parameters (urine volume, osmolarity, sodium, chloride, potassium, calcium, phosphate, microalbumin, aldosterone, creatinine) between 7:00 am and 10:00 pm and between 10:00 pm and 7:00 am. RESULTS: During the nighttime, volume (P=0.006), sodium (P=0.009), and chloride excretion (P=0.001) were significantly higher, and osmolarity (P=0.025) was significantly lower in patients as compared to controls. In comparing daytime to nighttime, controls showed the physiological reduced nocturnal excretion of volume (P=0.009) and chloride (P=0.023), and an increased osmolarity (P=0.026), but patients showed similar excretion rates of these parameters (all differences ns). CONCLUSIONS: These data indicate a loss of normal circadian profile of urine excretion in iRLS. The elevated nighttime excretion, with values similar to those in the daytime, hint at a possibly elevated fluid, sodium, and chloride intake during daytime.

Hypertrophic chronic pachymeningitis as a localized immune process in the craniocervical region.

Hypertrophic chronic pachymeningitis (HCP) is a rare disorder that causes intracranial or spinal thickening of the dura mater. This report describes a patient with progressive HCP in the craniocervical region associated with signs of rheumatic disease. A ventricular-atrial shunt had to be inserted because of increased intracranial pressure. The patient improved after suboccipital craniotomy, C1 to C6 laminectomy, and removal of the thickened dura. Additional therapy with methotrexate stopped progression, which was documented by MRI and PET.

Neurological monitoring of neurotoxicity induced by paclitaxel/cisplatin chemotherapy.

To evaluate the neurotoxicity of paclitaxel/cisplatin chemotherapy, we studied neurological and electrophysiological functions in 14 patients who had been treated with 1-7 courses of paclitaxel/cisplatin. The cumulative paclitaxel and cisplatin doses ranged from 175 to 1225 mg/m2 and 100-700 mg/m2, respectively. Neurological examinations as well as motor nerve conduction studies of the peroneal nerve were performed and summarised by means of a peripheral neuropathy score. Neurotoxicity with onset usually after the second treatment cycle occurred in 13 patients. 12 patients complained about sensory symptoms, 13 patients had impaired vibration sense and 8 patients developed additional muscle weakness, predominantly of the legs. Dysfunction of peroneal motor nerve conduction occurred in 13 patients. Reduction of amplitudes as well as slowing of conduction velocities were seen in 13 patients and prolonged distal latencies in 10 patients. The peripheral neuropathy score was elevated in 13 patients. Neurological symptoms, impairment of both vibration sense and tendon reflexes, and the peripheral neuropathy score increased with the cumulative doses of paclitaxel/cisplatin. Serial analysis among selected patients also revealed an increase in neurotoxicity with increasing cumulative drug doses. These data indicate the development of neurotoxicity in most patients treated with paclitaxel/cisplatin and also suggest that early signs of neurotoxicity can be detected by clinical examination with emphasis on symptoms as well as vibration sense and can be well documented by electrophysiological investigations.

Gangliosides in rabbit and human skeletal muscle with denervation atrophy.

In experimental denervation of rabbit skeletal muscle, an increase of gangliosides has been reported. Ganglioside, DNA, total lipid and protein levels were studied in experimental denervation of rabbit gastrocnemius muscle and in human skeletal muscle with denervation atrophy. In severe human denervation atrophy total ganglioside, DNA and total lipid levels were increased, and protein levels decreased as compared with controls. The ganglioside pattern was changed in severe human denervation atrophy and showed a significant increase of a GT1b-like and moderate decrease of a GM1-like compound. Findings in experimentally denervated rabbit muscle resembled results obtained in human denervation atrophy, showing a significant increase of total ganglioside levels as well as a moderate increase of GT1b-like and decrease of GM1-like compounds.

Botulinum toxin in the treatment of rare head and neck pain syndromes: a systematic review of the literature.

BACKGROUND: Botulinum neurotoxin (BoNT) is used to treat various neurological disorders associated with pathologically increased muscle tone. Botulinum toxin inhibits the release of the neurotransmitter acetylcholine at the neuromuscular junction thereby inhibiting striatal muscle contractions. Besides the reduction in muscle tone BoNT tends to reduce pain in pain syndromes associated with muscle spasm. In addition, BoNT has been proposed as an analgesic, suggesting alternative non-cholinergic mechanisms of action.Surprisingly, BoNT was reported as a potential treatment for tension-type headache and migraine-both primary headache syndromes without an apparent muscular component-however, varying responses to BoNT have been found, overall without sufficient evidence for a general treatment. In this systematic review we set out to clarify the efficacy and safety of BoNT in the treatment of rare head and neck pain syndromes (e. g. cervicogenic headache, chronic paroxysmal hemicrania, cluster headache, trigeminal neuralgia, temporomandibular disorders, cervical dystonia and whiplash injuries). OBJECTIVES: To assess the analgesic efficacy and safety of botulinum toxins versus other medicines, placebo or no treatment in rare head and neck pain syndromes. SEARCH STRATEGY: We searched the bibliographic databases MEDLINE, EMBASE and PASCAL Biomed to May 2003. We also reviewed the reference lists from identified articles including reviews and meta-analyses of treatment studies. Furthermore we searched booklets of scientific congresses in the field of neurology for potentially relevant studies. Additional reports were identified from the reference list of the retrieved papers, and by contacting experts in the field. SELECTION CRITERIA: Randomized controlled trials (RCTs) with any dose of BoNT for rare head and neck pain syndromes, describing subjective pain assessment as either the primary or a secondary outcome, were included in this review. DATA COLLECTION AND ANALYSIS: All trials were quality scored and two independent reviewers extracted data. Results were compared for differences, and discrepancies were resolved by discussion. MAIN RESULTS: Fourteen RCTs of BoNT in cervical dystonia were included in this review. All except one showed significant pain relief following BoNT treatment compared to placebo. Studies providing dichotomous outcome data were pooled using the Peto method. The overall effect was found to be highly significant (OR 4.795 [95% CI 5.551-6.473]). For cervicogenic headache, two RCTs-one positive study and one negative study-were included. Two studies addressing chronic neck pain were included in this review. Both studies did not reveal significant effects. Furthermore, one small trial (N = 15 patients) focussing BoNT in temporomandibular disorders was included,without demonstrating significant effectiveness but a high proportion of patients lost to follow-up and a high rate of adverse effects. For the use of BoNT in cluster headache, chronic paroxysmal hemicrania and trigeminal neuralgia no RCTs were identified. Adverse effects (AEs) were found to be mild to moderate and dose-dependent. They were summarized where possible, irrespective of the formulation used and condition treated (OR = 5.066 [95% CI 2.770-9.265], number-needed-to-harm (NNH) = 5.5 [range 4.4-17]). REVIEWERS' CONCLUSIONS: There is convincing evidence for the effectiveness of BoNT in the treatment of pain associated with cervical dystonia. Due to the frequent adverse effects predominantly observed with higher doses, the trade off in risk and benefit should be carefully considered in each case. For all other rare head and neck pain syndromes we found no RCTs (cluster headache, chronic paroxysmal hemicrania, trigeminal neuralgia) and only a few small sized trials (cervicogenic headache, chronic neck pain, temporomandibular disorders). We were therefore unable to draw any definite conclusions.

Spinal cavernous haemangioma (intradural-extramedullary) underlying repeated subarachnoid haemorrhage.

Within a period of 13 months a 24-year-old male student experienced four attacks of subarachnoid haemorrhage. An intradural-extramedullary haemangioma at the level of the second thoracic segment was found to be the cause of the repeated bleeding.

Efficacy and safety of a standardised 500 unit dose of Dysport (clostridium botulinum toxin type A haemaglutinin complex) in a heterogeneous cervical dystonia population: results of a prospective, multicentre, randomised, double-blind, placebo-controlled, parallel group study.

Results from a dose-ranging study in a selected group of de novo patients with rotational cervical dystonia (CD) suggest that 500 units of Dysport (Clostridium botulinum toxin type A haemaglutinin complex) is the optimal starting dose. The present study aimed to confirm the efficacy and safety profile of this dose in a population of CD patients more representative of those seen in a typical dystonia clinic. A total of 68 patients with moderate to severe CD (Tsui score > or = 9) were randomly assigned to receive placebo or Dysport 500 units. Treatment was administered according to the clinical pattern of head deviation, using a standardised injection protocol. A total of 21 patients (11 Dysport, 10 placebo) had not previously received botulinum toxin type A (BtxA) injections, and 47 patients (24 Dysport, 23 placebo) had received BtxA more than 12 weeks previously. Assessments were performed at baseline and weeks 4, 8 and 16. Patients defined as non-responders at week 4 were re-treated in an open phase with 500 units of Dysport at week 6, and were followed up at week 10. Significant between-group differences in Tsui scores were present at weeks 4 (p=0.001) and 8 (p=0.002). Similarly, there were significant between-group differences (p < 0.001) in patient and investigator assessments of response in favour of Dysport at weeks 4 and 8. Also, more Dysport (49%) than placebo (33%) patients were pain-free at week 4 (p=0.02). Overall, 30/35 (86 %) Dysport patients and 14/33 (42%) placebo patients were classified as responders at week 4. Adverse events were reported by 15/35 Dysport patients and 9/33 placebo patients. Open phase treatment produced improvements in Tsui (p < 0.001) and pain scores (p=0.011), and 23/24 patients were classified as responders. Although individual dose titration and muscle selection is desirable, this study demonstrated that a dose of 500 units of Dysport injected into clinically identified neck muscles without electromyographic guidance is safe and effective in the treatment of patients with the major clinical types of cervical dystonia.