A population based study of intracranial arachnoid cysts: clinical and neuroimaging outcomes following surgical cyst decompression in adults

Background

We have gradually adopted a liberal attitude towards surgical decompression of arachnoid cysts. This study describes the results from our institution.

Methods

Long term clinical and neuroimaging results of 156 adult patients (aged ⩾16 years) operated on for arachnoid cysts in our department during the period January 1987 to September 2004 were assessed based on their medical and neuroimaging records, and on a questionnaire.

Results

The clinical and/or neuroimaging results indicated that the cyst was successfully decompressed in all patients. 82% of patients were asymptomatic or had insignificant complaints at follow‐up. 12% reported no symptom relief whereas 6% experienced worsening of symptoms. The cyst disappeared after surgery, or was reduced to <50% of the preoperative volume, in 66% of cases. In another 24%, the postoperative volume was also reduced, but was larger than 50% of the original cyst volume. No reduction in fluid volume was observed in 10% of cases. There was no association between volume reduction and clinical improvement. A complication occurred in 26 patients (17%), all with temporal cysts, leading to reoperation in 11 patients (7.1%). In only two patients did the complication cause a permanent slight disability.

Conclusion

Decompression of arachnoid cysts yields a substantial clinical benefit with a low risk of severe complications.Arachnoid cysts are benign congenital malformations of the arachnoid. They can be located along the craniospinal axis, with a predilection for the temporal fossa.¹ They may present with specific symptoms, such as sensorimotor symptoms corresponding to the location of the cyst, but more often they yield unspecific symptoms (eg, headache or dizziness, or symptoms related to suboptimal cerebral function, such as epilepsy or impaired cognition).^{2,3,4,5,6,7,8,9,10}The treatment of such cysts, particularly in the majority of the patients with moderate and unspecific symptoms, has been controversial.^{11,12,13,14,15} Many authors have expressed a reluctance to operate on these patients unless the symptoms are dramatic. This was also the initial attitude of the senior author. However, based on several observations of our own and those of others, we have gradually changed our view. When we encountered patients that were severely impaired, with symptoms such as headache or dizziness, and who also had radiologically expansive cysts, we found it logical to attempt to alleviate the complaints by surgical cyst decompression. It has been our accumulated experience that surgical decompression yields clinical improvement in most patients with arachnoid cysts. Also, a growing literature indicates that cyst decompression improves the function of neighbouring cerebral tissue, thus supporting the view that patients with unspecific symptoms and “clinically silent” cysts may also profit from surgical cyst decompression.^{4,6,7,8,9,10,16}Treating a benign condition that is not life threatening with surgery, with the aim of improving quality of life, can only be justified when a clear clinical benefit, and no severe complications, can be demonstrated. We therefore wished to describe our experience with a relatively liberal indication for surgical decompression of intracranial arachnoid cysts. We have recently published a similar study on our paediatric cyst patients.¹⁷     

Influence of cognitive impairment on the institutionalisation rate 3 years after a stroke

Background and purpose

Pre‐existing cognitive decline and new‐onset dementia are common in patients with stroke, but their influence on institutionalisation rates is unknown.

Objective

To evaluate the influence of cognitive impairment on the institutionalisation rate 3 years after a stroke.

Design

(1) The previous cognitive state of 192 consecutive patients with stroke living at home before the stroke (with the Informant Questionnaire on COgnitive Decline in the Elderly (IQCODE)), (2) new‐onset dementia occurring within 3 years and (3) institutionalisation rates within 3 years in the 165 patients who were discharged alive after the acute stage were prospectively evaluated.

Results

Independent predictors of institutionalisation over a 3‐year period that were available at admission were age (adjusted odds ratio (adjOR) for 1‐year increase  = 1.08; 95% confidence interval (CI) 1.03 to 1.15), severity of the neurological deficit (adjOR for 1‐point increase in Orgogozo score = 0.97; 95% CI 0.96 to 0.99) and severity of cognitive impairment (adjOR for 1‐point increase in IQCODE score = 1.03; 95% CI 1 to 1.06). Factors associated with institutionalisation at 3 years that were present at admission or occurred during the follow‐up were age (adjOR for 1‐year increase = 1.17; 95% CI 1.07 to 1.27) and any (pre‐existing or new) dementia (adjOR = 5.85; 95% CI 1.59 to 21.59), but not the severity of the deficit of the neurological deficit.

Conclusion

Age and cognitive impairment are more important predictors of institutionalisation 3 years after a stroke than the severity of the physical disability.Institutionalisation after a stroke increases with the severity of the neurological deficit, increasing age, female gender, low socioeconomic level, marital status and poor social environment.^1,2,3,4,5,6Dementia is common after a stroke,⁷ leading to autonomy loss.⁸ Pre‐existing dementia is present in up to 16% of patients with stroke,^9,10,11,12 and post‐stroke de mentia (PSD) occurs in up to one third.⁷ Several studies have found a link between cognitive impairment and institutionalisation after a stroke,^1,2,3,4,5 but they had several methodological limitations: (1) cross‐sectional studies were performed in long‐term stroke survivors and did not take into account patients who had been institutionalised but died before the study⁶; (2) there was no systematic cognitive assessment¹³ or only a Mini Mental State Examination,¹⁴ which is not appropriate for patients with stroke; and (3) most studies included only patients recruited in rehabilitation centres, leading to selection bias.^1,2,3,4,5 To our knowledge, no study has prospectively evaluated the influence of pre‐existing cognitive impairment and PSD on the institutionalisation rate after a stroke.The aim of this study was to evaluate the influence of the previous cognitive state and new‐onset dementia on the institutionalisation rate 3 years after a stroke.     

Intake of polyunsaturated fatty acids and vitamin E reduces the risk of developing amyotrophic lateral sclerosis

Background

To assess whether the premorbid dietary intake of fatty acids, cholesterol, glutamate or antioxidants was associated with the risk of developing amyotrophic lateral sclerosis (ALS).

Methods

Patients referred to our clinic during 2001–2002, who had definite, probable or possible ALS according to El Escorial criteria, without a familial history of ALS, were asked to participate in a case–control study (132 patients and 220 healthy controls). A food‐frequency questionnaire was used to assess dietary intake for the nutrients of interest. Multivariate logistic regression analysis was performed with adjustment for confounding factors (sex, age, level of education, energy intake, body mass index and smoking).

Results

A high intake of polyunsaturated fatty acid (PUFA) and vitamin E was significantly associated with a reduced risk of developing ALS (PUFA: odds ratio (OR) = 0.4, 95% confidence interval (CI) = 0.2 to 0.7, p = 0.001; vitamin E: OR = 0.4, 95% CI = 0.2 to 0.7, p = 0.001). PUFA and vitamin E appeared to act synergistically, because in a combined analysis the trend OR for vitamin E was further reduced from 0.67 to 0.37 (p = 0.02), and that for PUFA from 0.60 to 0.26 (p = 0.005), with a significant interaction term (p = 0.03). The intake of flavonols, lycopene, vitamin C, vitamin B₂, glutamate, calcium or phytoestrogens was not associated with the risk of developing ALS.

Conclusion

A high intake of PUFAs and vitamin E is associated with a 50–60% decreased risk of developing ALS, and these nutrients appear to act synergistically.Sporadic amyotrophic lateral sclerosis (ALS) probably develops through the combined effects of several modifying genes and environmental factors.¹ Despite several studies that investigated environmental exposures in relation to ALS, age, gender and smoking are the only established risk factors.² Several, not mutually exclusive, pathological processes may contribute to motor neurone death in ALS in a so‐called convergence model,³ including oxidative stress, mitochondrial dysfunction, protein misfolding, axonal strangulation, apoptosis, inflammation, glutamate excitotoxicity and defects in neurotrophin biology. Nutrients are factors that could influence these processes and thereby the risk of developing ALS or its clinical expression.ALS was previously found to be positively associated with intake of glutamate,⁴ fat,⁴ fish⁵ and milk,^6,7 and inversely associated with intake of lycopene,⁸ dietary fibre,⁴ bread and pasta.⁹ Two other studies, however, failed to establish the relationship with milk.^10,11 Several of these studies included only small samples of patients (<25),^5,6,9 or investigated nutrition as one of many environmental factors, thus increasing the likelihood of chance findings.^{5,6,7,9,10,11} Furthermore, most studies did not account for the possible influence of clinical onset preceding the diagnosis^{5,6,7,8,9,10,11} or adjust for possible confounders including total energy intake, body mass index (BMI), sex, smoking and education.^{5,6,7,9,10,11}One study found an association between intake of total fat and ALS, although this was not hypothesised beforehand.⁴ This finding is of interest considering the observed associations of intake of saturated and unsaturated fatty acids and cholesterol with other neurodegenerative diseases.¹² In this case–control study, therefore, we examined the possible association between premorbid dietary intake of fatty acids, cholesterol, glutamate, phytoestrogens, calcium and anti‐oxidants and the risk of developing ALS, adjusting for confounding factors.     

Fatigue and activity dependent changes in axonal excitability in amyotrophic lateral sclerosis

Background

While patients with amyotrophic lateral sclerosis (ALS) may complain of fatigue, the underlying mechanisms appear complex, with dysfunction of central and peripheral nervous systems independently reported as contributing factors. The aim of the present study was to further delineate the mechanisms underlying increased fatigability in ALS by measuring activity dependent changes in axonal excitability following a maximum voluntary contraction (MVC).

Methods

Nerve excitability changes were recorded before and after an MVC of the abductor pollicis brevis in 16 patients with ALS and 25 controls.

Results

In patients with ALS, there was a greater increase in threshold (36.5 (5.9)%; controls 19.6 (3.5)%; p<0.05) as a result of MVC, with reduction in the amplitude of the compound muscle action potential generated by a submaximal stimulus (ALS 49 (7.6)%; controls 41.0 (5.4)%). These changes were associated with an increase in superexcitability (ALS 65.1 (25.4)%; controls 42.3 (5.7)%) and reduction in strength–duration time constant (ALS 20 (4.9)%; controls 10 (2.5)%; p<0.01), indicative of axonal hyperpolarisation. The increase in threshold was more pronounced in patients with ALS with predominantly lower motor neuronal involvement.

Conclusions

Higher firing rates of surviving motor axons attempting to compensate for neurogenic weakness are likely to explain the greater activity dependent changes in ALS. As such, the present study suggests a further peripheral factor underlying the development of fatigue in ALS.Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that affects motor neurones in the spinal cord, brainstem and motor cortex.^1,2 The consequences of this neurodegeneration are motor deficits in the limbs, bulbar and respiratory muscles.³ Although the mechanisms of neuronal dysfunction, and ultimately the development of symptoms in ALS, remain unknown, glutamate excitotoxicity,^4,5,6 increased levels of inducible nitric oxide synthase levels⁴ and, in cases of inherited ALS, oxidative stress secondary to mutations in the superoxide dismutase‐1 gene, have been proposed.^7,8,9,10Increased fatigability, defined as an inability to sustain a predictable maximal force during voluntary contraction, is a common symptom of ALS.^11,12,13 The mechanisms underlying fatigue in ALS are complex, and contributions from both the central and peripheral nervous systems have been reported.^11,12 Central fatigue refers to a reduced excitatory drive to motor neurones, secondary to central nervous system dysfunction, resulting in incomplete motor unit recruitment and submaximal motor unit discharge rates. In contrast, peripheral fatigue typically refers to impaired muscle activation, caused by dysfunction at or below the anterior horn cell.^13,14 Perhaps somewhat counterintuitively, fatigue in ALS appears to be independent of muscle strength and disease severity.^15,16 Regardless of the underlying mechanism, fatigue in ALS severely impacts on the patient''s quality of life.^15,16The ability to sustain a motor output may be assessed by measuring changes in axonal membrane threshold following a voluntary contraction. Specifically, in peripheral nerves, voluntary contraction activates the axonal membrane Na⁺/K⁺ pump,¹⁷ which attempts to return the resting membrane potential to baseline after contraction has ceased,^18,19,20,21 resulting in activity dependent hyperpolarisation. The magnitude of activity dependent hyperpolarisation is determined by the impulse load²² and, in neurological diseases where the safety margin for impulse conduction has been reduced as occurs for instance in demyelinating neuropathy, may be sufficient to induce conduction failure.^23,24,25 In an attempt to further delineate the mechanisms underlying fatigability and weakness in ALS, the present study measured activity dependent changes in axonal excitability induced by voluntary contraction.     

Cerebral venous thrombosis and plasma concentrations of factor VIII and von Willebrand factor: a case control study

Background

High plasma concentrations of factor VIII (FVIII) and von Willebrand factor (VWF) have been recently associated with a moderately increased risk of venous thrombosis, but their roles in cerebral sinus and venous thrombosis (CSVT) have not been addressed. To determine whether elevation of FVIII and VWF is more frequent in CSVT, we analysed plasma levels of FVIII and VWF in a case control study.

Methods

The study population consisted of 25 consecutive patients (of whom nine were excluded) admitted for CSVT to the Department of Neurology, Amiens University Hospital, France, from January 1997 to December 2002, for a general screening for thrombophilia. Sixty‐four healthy subjects matched for age and sex formed the group control.

Results

Mean FVIII (CSVT: 167.3 (SD 48.8) IU/dl; control group: 117.9 (39.8) IU/dl; p = 0.001) and VWF levels (CSVT: 165.4 (76.5)%; control group: 108.5 (27.8)%; p = 0.01) were significantly higher in the CSVT group. Using the 95th percentile of the control group as the cut off value, elevated FVIII (>190 IU/dl) occurred in 25% (4/16) (p = 0.005) and elevated VWF (>168%) in 37.5% (6/16) of patients with CSVT (p<0.001). Using previously reported cut off values (>150 IU/dl or >150%) showed the same results (FVIII: p = 0.005; VWF: p = 0.009).

Conclusion

Our study suggests that elevation of plasma factor VIII levels is the most common prothrombotic risk factor for CSVT. Elevation of VWF is also associated with an increased risk of CSVT but its effect seems to be partly mediated through FVIII.Cerebral sinus and vein thrombosis (CSVT) is a rare localisation of venous thromboembolic disease. It generally occurs in young or middle‐aged adults and accounts for approximately 1% of strokes.¹ Many coagulation disorders have been associated with CSVT.^2,3,4Several prospective studies showed that high concentrations of factor VIII (FVIII) are associated with a moderately increased risk of venous thromboembolism (VTE).^5,6 The role of increased levels of von Willebrand Factor (VWF) in VTE remains unclear.^5,7 Recent studies suggest that the effect of VWF is fully explained by FVIII concentrations.⁵ Indeed, the ABO blood group, which regulates plasma concentrations of both FVIII and VWF, may also play a role in susceptibility to thrombosis.^8,9,10The increased risk of VTE with elevated levels of FVIII or VWF has been observed in previous studies.^5,6,7,11 However, they did not specifically include patients with CSVT^7,9 or they were incomplete.¹²The aim of our study was to assess plasma levels of FVIII, VWF and other thrombophilic factors in patients with CSVT in a case control study.     

Long term follow-up of the first 70 operated adults in the Goteborg Epilepsy Surgery Series with respect to seizures, psychosocial outcome and use of antiepileptic drugs

Objective

To compare long term (10 years) seizure outcome, psychosocial outcome and use of antiepileptic drugs (AED) with the 2 year follow‐up in adults after resective epilepsy surgery.

Methods

All adults (n = 70) who underwent resective epilepsy surgery from 1987 to 1995 in the Göteborg Epilepsy Surgery Series were included. Fifty‐four had undergone temporal lobe resections and 16 extratemporal resections (12 frontal). A cross‐sectional follow‐up in the form of a semistructured interview was performed in late 2003.

Results

Mean follow‐up was 12.4 years (range 8.6–16.2). Of the 70 patients (51% males), five (7%) were dead (three as a result of non‐epilepsy related causes). Of the 65 patients interviewed, 38 (58%) were seizure‐free at the long term follow‐up: 65% of the patients with temporal lobe resections and 36% of the patients with extratemporal resections. Of the 35 patients who were seizure‐free at the 2 year follow‐up, 3 (9%) had seizures at the long term follow‐up. Of the 30 patients who had seizures at the 2 year follow‐up, 6 (20%) were seizure‐free at the long term follow‐up. Of all 65 patients, 45 (69%) had the same seizure status as the 2 year follow‐up. Sixteen (25%) had an improved seizure status and 4 (6%) had a worsened status. Of the seizure‐free patients, 11 (29%) had ceased taking AED, 28 (74%) were working and 25 (66%) had a driving license.

Conclusions

Adult patients who are seizure‐free 2 years after resective epilepsy surgery are most likely to still be seizure‐free 10 years later. Most are working and have obtained a driving license.Epilepsy surgery is a well established treatment for medically intractable epilepsy.^1,2 The ultimate aims of epilepsy surgery are to reduce the frequency and intensity of seizures and thereby to improve quality of life. Most studies of the effectiveness of epilepsy surgery have focused on seizure outcome of anterior temporal lobe resections 1–2 years after surgery. One randomised controlled study² and multiple clinical series have shown that approximately two thirds of patients become free of seizures with impairment of awareness. It has also been shown that quality of life scores improve after temporal lobe resection, especially in seizure‐free patients who also have a trend towards better social function (see Engel et al,³ Jones et al⁴ and Malmgren et al⁵).Concern has been raised about the long term seizure outcome of epilepsy surgery. Several studies have described late seizure recurrences after initial success, sometimes but not always related to discontinuation of antiepileptic drugs (AED).^6,7,8 On the other hand, it has been suggested that seizure outcome at 2 years after surgery in patients subjected to temporal lobectomy predicts the long term outcome.^6,9,10,11,12However, there are only a few studies concerning long term outcome beyond 5 years (ie, presenting data with 10 years of follow‐up).¹³ Most have only included patients subjected to temporal lobectomy and very little is known about the long term seizure outcome for patients who have undergone other resection types.Patients'' aims for epilepsy surgery are, however, not limited to seizure relief. The five commonest aims for patients during presurgical evaluation cited in the study by Taylor et al¹⁴ were: desire for work, driving of motor vehicles, independence, socialising and freedom from drugs (see also Gilliam et al¹⁵). Psychosocial outcomes (eg, employment status, educational status and driving a vehicle) are seldom reported in long term studies. Of the few studies reporting psychosocial aspects, the average follow‐up time is no more than 5 years and most of them have only included patients subjected to temporal lobectomy^4,16,17,18 (see Guldvog et al¹⁹).The Göteborg Epilepsy Surgery Series is a multidisciplinary prospective follow‐up of all patients subjected to epilepsy surgery in Göteborg since its start in 1987. We have previously described the 2 year outcome regarding alterations in seizure frequency,²⁰ general cognitive function, and memory²¹ and psychiatric morbidity²² in the first 70 consecutive operated adults. The aim of this study was to compare the long term (>10 years) outcome concerning seizure status, psychosocial issues and use of AED with the 2 year follow‐up in these well characterised 70 adults.     

Apolipoprotein E epsilon4 and impaired episodic memory in community-dwelling elderly people: a marked sex difference. The Hordaland Health Study

Background

Among elderly people without dementia, the apolipoprotein E ε4 allele (APOE4) has been associated with cognitive deficit, particularly in episodic memory, but few reports are available on whether this association differs by sex.

Methods

In a community‐dwelling Norwegian cohort of 2181 elderly people (55% women), aged 70–74 years, episodic memory was examined in relation to sex and APOE4 zygosity, with the Kendrick Object Learning Test (KOLT).

Results

Possession of at least one APOE4 allele had a modest, detrimental effect on episodic memory in women, whereas in men, heterozygotes were unaffected and homozygotes had markedly lower scores across the distribution of KOLT scores. This sex difference was found consistently in all analyses: on comparing means and medians, examining trends across quintiles, and studying the distribution of scores and the risk of cognitive impairment. Results were broadly similar when adjusted for known determinants of cognition and also when severely impaired participants were excluded. The adjusted odds ratio (OR) of cognitive impairment in women was shown to be 1.8 (95% confidence interval (CI): 1.1 to 2.8) for heterozygotes and 1.1 (0.3 to 3.7) for homozygotes; the adjusted OR in men was observed to be 1.1 (0.6 to 2.1) for heterozygotes and 10.7 (4.7 to 24) for homozygotes.

Conclusions

Although the harmful effect of APOE4 on episodic memory was modest in women, the risk was found to occur in about 30%. APOE4 was observed to have a dramatic effect on episodic memory in men, but only in homozygotes, who comprised about 3% of men: the whole male homozygous group showed a marked shift to lower memory scores.Age and the apolipoprotein E ε4 allele (APOE4) are the most important known risk factors for sporadic Alzheimer''s disease. The disease is thought to have a long presymptomatic phase,¹ which suggests that APOE4 starts exerting its detrimental effects in the preclinical phase. Most studies on elderly people without dementia have found that the APOE4 allele is associated with various cognitive deficits,^{2,3,4,5,6,7,8,9,10,11,12,13,14} particularly in memory.^2,3,4,5,6,7 A recent meta‐analysis of more than 20 000 people concluded that this allele was associated with poorer performance on tests of global cognitive functioning, episodic memory and executive functioning.¹⁵The association of APOE4 with Alzheimer''s disease varies with sex.^{16,17,18,19,20} The meta‐analysis by Farrer et al²⁰ found that APOE4 homozygosity affords a high risk of Alzheimer''s disease for both men and women, but that a single copy of the allele confers a greater risk on women than on men. A similar sex difference related to APOE4 has been found in the degree of hippocampal atrophy in a cohort with mild cognitive impairment.²¹ We may therefore expect to find an effect related to sex of the APOE4 allele in cognitive tests in elderly people without dementia. Two studies^3,22 that have reported an influence of sex on this relationship found a stronger effect of APOE4 in women.^3,22In this study, we investigated whether sex influences the relationship between APOE alleles and episodic memory in community‐dwelling elderly people. We selected episodic memory because memory deficit is a hallmark of Alzheimer''s disease. Tests of episodic memory have been found to be particularly effective in identifying people at risk.^23,24 We compared the influence of sex in our cohort with that found on the risk of Alzheimer''s disease. We studied a relatively large group of 2181 people from western Norway.     

Cognitive outcome in adults after bacterial meningitis

Objective

To evaluate cognitive outcome in adult survivors of bacterial meningitis.

Methods

Data from three prospective multicentre studies were pooled and reanalysed, involving 155 adults surviving bacterial meningitis (79 after pneumococcal and 76 after meningococcal meningitis) and 72 healthy controls.

Results

Cognitive impairment was found in 32% of patients and this proportion was similar for survivors of pneumococcal and meningococcal meningitis. Survivors of pneumococcal meningitis performed worse on memory tasks (p<0.001) and tended to be cognitively slower than survivors of meningococcal meningitis (p = 0.08). We found a diffuse pattern of cognitive impairment in which cognitive speed played the most important role. Cognitive performance was not related to time since meningitis; however, there was a positive association between time since meningitis and self‐reported physical impairment (p<0.01). The frequency of cognitive impairment and the numbers of abnormal test results for patients with and without adjunctive dexamethasone were similar.

Conclusions

Adult survivors of bacterial meningitis are at risk of cognitive impairment, which consists mainly of cognitive slowness. The loss of cognitive speed is stable over time after bacterial meningitis; however, there is a significant improvement in subjective physical impairment in the years after bacterial meningitis. The use of dexamethasone was not associated with cognitive impairment.The estimated annual incidence of bacterial meningitis is 4–6 per 100 000 adults and Streptococcus pneumoniae (pneumococcus) and Neisseria meningitidis (meningococcus) are the causative bacteria in 80% of cases.^1,2 Fatality rates in patients with pneumococcal meningitis (26%) and meningococcal meningitis (7%) are significant.^1,2,3 Even in patients with apparent good recovery, cognitive impairment occurs frequently,⁴ especially after pneumococcal meningitis.^4,5,6 The cognitive functions affected by bacterial meningitis differ between studies, most likely because of the limited numbers of patients examined, and the lack of uniformity across studies in assessment methods and in the definition of cognitive impairment.^{4,5,6,7,8,9,10} We therefore pooled data on cognitive outcome after bacterial meningitis from three of our previous studies to more clearly determine which cognitive functions are affected by bacterial meningitis and to identify which patients are at risk of developing cognitive impairment.     

Deep-brain stimulation: long-term analysis of complications caused by hardware and surgery--experiences from a single centre

Objective

To determine the surgery‐related and hardware‐related complications of deep‐brain stimulation (DBS) at a single centre.

Methods

262 consecutive patients (472 electrodes) operated for DBS in our department from February 1996 to March 2003 were retrospectively analysed to document acute adverse events (30 days postoperatively). The data of 180 of these patients were additionally revised to assess long‐term complications (352 electrodes, mean follow‐up 36.3 (SD 20.8) months).

Results

The frequency of minor intraoperative complications was 4.2% (11/262 patients). Transient (0.2%) or permanent (0.4%) neurological deficits, and in one case asymptomatic intracranial haemorrhage (0.2%), were registered as acute severe adverse events caused by surgery. Among minor acute complications were subcutaneous bleeding along the extension wire (1.2%) and haematoma at the pulse generator implantation site (1.2%). Skin infection caused by the implanted material was registered in 15 of 262 patients (5.7%). The infection rate during the first observation period was 1.5% (4/262 patients) and the late infection rate was 6.1% (11/180 patients). Partial or complete removal of the stimulation system was necessitated in 12 of 262 (4.6%) patients because of skin infection. During the long‐term observation period, hardware‐related problems were registered in 25 of 180 (13.9%) patients.

Conclusions

Stereotactic implantation of electrodes for DBS, if performed with multiplanar three‐dimensional imaging and advanced treatment planning software, is a safe procedure with no mortality and low morbidity. The main causes for the patients'' prolonged hospital stay and repeated surgery were wound infections and hardware‐related complications.During the past 10 years, worldwide, a growing number of patients with movement disorders have been treated with deep‐brain stimulation (DBS). The most frequent indications were Parkinson''s disease, tremor and dystonia. At present, new indications such as obsessive–compulsive disorders (OCD), Gilles‐de‐la‐Tourette syndrome, severe depression or epilepsy are under investigation.^1,2,3,4,5DBS is now considered to modulate the functional units of the CNS, serving as a permanent and lifelong treatment. Therefore, a realistic analysis of complications should not be restricted to acute hardware‐related and surgery‐related adverse events, but should also document problems occurring in the long term. In the literature, a reasonably high number of publications have already dealt with the adverse events associated with DBS. Only a few studies, however, analysed a larger number of patients (n>50),^{6,7,8,9,10,11} and some of this work considered only one possible source for complications, either surgery^6,10 or the implanted hardware.^8,9 In this article, we present a comprehensive analysis of 262 patients of a single centre (Department of Stereotaxy and Functional Neurosurgery, University of Cologne, Cologne, Germany).     

Co-occurrence of affective and schizophrenia spectrum disorders with PINK1 mutations

Objective

To investigate a possible association of mutations in the PTEN‐induced putative kinase 1 (PINK1) gene with psychiatric disorders in a large family with monogenic parkinsonism.

Method

20 members of a family (4 homozygous, 11 heterozygous and 5 non‐mutation carriers) were investigated for the presence of psychiatric disorders using the structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, 4^th edition (DSM‐IV); information on three additional heterozygous mutation carriers was obtained according to the family history research diagnostic criteria.

Results

We found predominantly affective and schizophrenia spectrum disorders in 11 (61%) of the 18 mutation carriers and in 1 (20%) of the 5 mutation‐negative cases.

Conclusions

First, affective and psychotic symptoms may be part of the phenotypic spectrum or even the sole manifestation of PINK1 mutations. Second, patients with familial movement disorders associated with psychiatric conditions may serve as a valuable study population to explore (genetic) causes of neuropsychiatric disease.In patients with Parkinson''s disease (PD), a wide range of psychiatric disorders has been described including depression (20–50%),¹ psychosis (15–40%),^2,3 anxiety disorder (20–40%) and cognitive impairment (20%).² Psychiatric disorders may be the first or even the only manifestation in carriers of Parkin gene mutations, the most‐frequent known cause of early‐onset parkinsonism (EOP).⁴ Likewise, psychiatric problems have been reported in patients and their motor‐asymptomatic relatives with mutations in the recently detected PTEN‐induced kinase 1 (PINK1) gene, the second‐commonest cause of EOP.^5,6,7,8,9Two homozygous mutations in the PINK1 gene were initially described in three consanguineous families with EOP.⁶ The frequency of PINK1 mutations ranges from 1% to 8% in patients with PD of different ethnicities who are often selected for young age of onset and for family history (for review see Klein and Schlossmacher¹⁰). Most of the currently described mutations are localised near or within the functional serine/threonine kinase domain of PINK1 and are expected to result in a loss‐of‐function effect in vivo. Wild‐type PINK1 functions as a protein kinase that is mainly located within the mitochondria.Although PINK1‐associated parkinsonism is generally considered an autosomal recessive condition, a growing body of evidence has been accumulating that supports the notion of a single heterozygous mutation conferring disease susceptibility in at least a subset of patients.^6,8,9,10,11Currently, no studies have systematically assessed psychiatric symptoms in monogenic EOP. To investigate this possible association, we evaluated a large family with EOP with PINK1 mutations for the presence of psychiatric disorders.     

Carotid body autotransplantation in Parkinson disease: a clinical and positron emission tomography study

Background

Carotid body (CB) glomus cells are highly dopaminergic and express the glial cell line derived neurotrophic factor. The intrastriatal grafting of CB cell aggregates exerts neurotrophic actions on nigrostriatal neurons in animal models of Parkinson disease (PD).

Objective

We conducted a phase I–II clinical study to assess the feasibility, long term safety, clinical and neurochemical effects of intrastriatal CB autotransplantation in patients with PD.

Methods

Thirteen patients with advanced PD underwent bilateral stereotactic implantation of CB cell aggregates into the striatum. They were assessed before surgery and up to 1–3 years after surgery according to CAPIT (Core Assessment Programme for Intracerebral Transplantation) and CAPSIT‐PD (Core Assessment Programme for Surgical Interventional Therapies in Parkinson''s Disease) protocols. The primary outcome measure was the change in video blinded Unified Parkinson''s Disease Rating Scale III score in the off‐medication state. Seven patients had ¹⁸F‐dopa positron emission tomography scans before and 1 year after transplantation.

Results

Clinical amelioration in the primary outcome measure was observed in 10 of 12 blindly analysed patients, which was maximal at 6–12 months after transplantation (5–74%). Overall, mean improvement at 6 months was 23%. In the long term (3 years), 3 of 6 patients still maintained improvement (15–48%). None of the patients developed off‐period dyskinesias. The main predictive factors for motor improvement were the histological integrity of the CB and a milder disease severity. We observed a non‐significant 5% increase in mean putaminal ¹⁸F‐dopa uptake but there was an inverse relationship between clinical amelioration and annual decline in putaminal ¹⁸F‐dopa uptake (r = −0.829; p = 0.042).

Conclusions

CB autotransplantation may induce clinical effects in patients with advanced PD which seem partly related to the biological properties of the implanted glomus cells.Parkinson disease (PD) is a progressive neurodegenerative disorder of unknown aetiology. Its main pathological hallmark is the degeneration of midbrain dopaminergic neurons projecting to the striatum, although other neuronal systems are also affected.¹ Current pharmacological and surgical therapies are symptomatically effective but their long term utility is limited because of disease progression.^2,3 Therefore, there is a need for neuroprotective and/or neurorestorative therapies capable of arresting or reversing the neurodegenerative process.Over the past two decades, cell replacement therapies have been tested in PD patients with the objective of restoring the striatal dopaminergic deficit.⁴ Transplantation of fetal mesencephalic neurons, the most frequently used technique, can increase the striatal dopamine storage, but does not always produce the expected clinical benefit and may induce disabling off‐medication dyskinesias.^5,6 Thus it appears that the ectopic placement of dopamine secreting cells in the striatum is not the ideal approach to compensate for progressive nigrostriatal neuronal loss.⁷ Given this scenario, the clinical applicability of other transplantation procedures based on a similar rationale (eg, intrastriatal grafting of porcine mesencephalic neurons, retinal pigment epithelial cells or stem cell derived dopaminergic neurons) is, for the moment, uncertain.More recently, other strategies aiming to protect or restore the nigrostriatal pathway have emerged. Glial cell line derived neurotrophic factor (GDNF) has been shown to exert neuroprotective and neurorestorative actions in animal models of PD.^8,9,10 The clinical efficacy of GDNF has been assayed in clinical trials, but the method of delivery is a critical issue. Whereas intraventricular administration failed to induce clinical benefit,¹¹ intraputaminal infusion showed promising results,^12,13 although a placebo controlled trial using this route has been halted because of lack of efficacy and safety concerns about recombinant human GDNF administration.¹⁴ Other alternative methods being tested experimentally in parkinsonian animals include in vivo gene therapy using GDNF encoding viral vectors^15,16,17 and the intrastriatal grafting of recombinant GDNF producing cell lines.^18,19,20,21 Carotid body (CB) glomus cells are neural crest derived dopaminergic cells that express high levels of GDNF. Glomus cell GDNF production is resistant to 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine administration, and maintained in aged rodents or after intrastriatal grafting.^22,23 The survival rate of these cells after transplantation (>70%) is particularly high as hypoxia stimulates their growth and function. Moreover, CB grafts performed in young rats remain active for the entire animal lifespan.^22,23 Transplantation of CB cell aggregates has been shown to induce a neurotrophic mediated recovery in animal models of PD^{22,23,24,25,26,27} and stroke.^28,29We conducted a phase I–II video blinded clinical study to assess the long term safety, clinical and neurochemical effects of intrastriatal CB autotransplantation in patients with advanced PD. In a pilot report of our first six patients, we showed this procedure to be feasible.³⁰ Here we report the clinical outcomes and prognostic factors in the whole study (n = 13), as well as ¹⁸F‐dopa positron emission tomography (PET) outcomes in a subgroup of patients (n = 7).     

Diffusion anisotropy of the cervical cord is strictly associated with disability in amyotrophic lateral sclerosis

Background

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with severe cervical cord damage due to degeneration of the corticospinal tracts and loss of lower motor neurones. Diffusion tensor magnetic resonance imaging (DT MRI) allows the measurement of quantities reflecting the size (such as mean diffusivity) and orientation (such as fractional anisotropy) of water‐filled spaces in biological tissues.

Methods

Mean diffusivity and fractional anisotropy histograms from the cervical cord of patients with ALS were obtained to: (1) quantify the extent of tissue damage in this critical central nervous system region; and (2) investigate the magnitude of the correlation of cervical cord DT MRI metrics with patients'' disability and tissue damage along the brain portion of the corticospinal tracts. Cervical cord and brain DT MRI scans were obtained from 28 patients with ALS and 20 age‐matched and sex‐matched controls. Cord mean diffusivity and fractional anisotropy histograms were produced and the cord cross‐sectional area was measured. Average mean diffusivity and fractional anisotropy along the brain portion of the corticospinal tracts were also measured.

Results

Compared with controls, patients with ALS had significantly lower mean fractional anisotropy (p = 0.002) and cord cross‐sectional area (p<0.001). Mean diffusivity histogram‐derived metrics did not differ between the two groups. A strong correlation was found between mean cord fractional anisotropy and the ALS Functional Rating Score (r = 0.74, p<0.001). Mean cord and brain fractional anisotropy values correlated moderately (r = 0.37, p = 0.05).

Conclusions

Cervical cord DT MRI in patients with ALS allows the extent of cord damage to be graded. The conventional and DT MRI changes found are compatible with the presence of neuroaxonal loss and reactive gliosis, with a heterogeneous distribution of the pathological process between the brain and the cord. The correlation found between cord fractional anisotropy and disability suggests that DT MRI may be a useful adjunctive tool to monitor the evolution of ALS.Amyotrophic lateral sclerosis (ALS) is the most common adult‐onset motor neurone disease, characterised by a progressive and simultaneous degeneration of upper and lower motor neurones.^1,2 In its typical form, the disease begins either in one limb or with a combination of bulbar and corticobulbar symptoms, and continues with progressive weakness of the bulbar, limb, thoracic and abdominal musculature.^1,2 By using a variety of conventional magnetic resonance imaging (MRI) sequences, several studies^{3,4,5,6,7,8,9,10,11,12,13,14,15} have shown changes in signal intensity along the brain portion of the corticospinal tracts, particularly in the posterior limb of the internal capsule and cerebral peduncles, varying between 25% and 80%. Reduced magnetisation transfer ratios in the internal capsule^8,11 and N‐acetylaspartate levels in the motor cortex^13,16,17 of patients with ALS have also been observed. However, none of these studies has reported a correlation between such magnetic resonance abnormalities and the degree of disability.^{8,11,13,16,17}Diffusion‐tensor magnetic resonance imaging (DT MRI) enables the random diffusional motion of water molecules to be measured and thus provides quantitative indices of the structural and orientational features of the central nervous system (CNS).¹⁸ DT MRI has been used to assess quantitatively the tissue damage of the brain portion of the corticospinal tracts in ALS,^{12,19,20,21,22,23} and all studies have shown increased mean diffusivity (indicating a loss of structural barriers limiting the motion of water molecules) and decreased fractional anisotropy (indicating a loss of tissue organisation). However, brain DT MRI studies also resulted in heterogeneous clinicopathological correlations, as some authors found a moderate correlation between brain DT MRI metrics and the severity of disability,^12,21,23 but others did not.¹⁹ In the past few years, DT MRI has also been used successfully to grade the extent of cervical cord damage associated with demyelinating conditions.^24,25,26Considering that the cervical cord in ALS is one of the most affected portions of the CNS (owing to the combined presence of neuronal loss in the anterior horns of the grey matter and degeneration of the corticospinal tracts), we obtained mean diffusivity and fractional anisotropy histograms of the cervical cord from patients with ALS with the following aims: (1) to quantify the extent of tissue damage in this critical CNS region; and (2) to investigate the magnitude of the correlation of cervical cord DT MRI metrics with patients'' disability and tissue damage along the brain portion of the corticospinal tracts.     

Axonal damage and outcome in subarachnoid haemorrhage

Background

On the basis of preliminary evidence from patients with subarachnoid haemorrhage (SAH), axonal degeneration is thought to be an underestimated pathological feature.

Methods

A longitudinal study in 17 patients with aneurysmal SAH. Ventricular CSF was collected daily for up to 14 days. The neurofilament heavy chain^SMI35 (NfH^SMI35, a biomarker for axonal damage) was quantified using a standard ELISA (upper limit of normal 0.73 ng/ml). The primary outcome measure was the Glasgow Outcome Score (GOS) at 3 months.

Results

Of 148 samples from patients with SAH, pathologically high NfH levels in the CSF were found in 78 (52.7%) samples, compared with 20 (5%) of 416 samples from the reference population (p<0.0001). A pathological increase in NfH was observed in all patients with a bad outcome (GOS 1–3) compared with 8% of those with a good outcome (GOS 4–5, p<0.0001). This increase typically became significant 7 days after the haemorrhage (p<0.01). The result was confirmed by analysing the individual mean NfH concentrations in the CSF (3.45 v 0.37 ng/ml, p<0.01), and was reinforced by the inverse correlation of NfH in the CSF with the GOS (r = −0.65, p<0.01). Severity of injury was found to be correlated to NfH^SMI35 levels in the CSF (World Federation of Neurological Surgeons, r = 0.63, p<0.01 and Glasgow Coma Score, r = −0.61, p<0.01).

Conclusion

Patients with SAH thus have secondary axonal degeneration, which may adversely affect their outcome.The presence of axonal degeneration in patients with subarachnoid haemorrhage (SAH) has recently been suggested in a longitudinal study.¹ One important finding was that damage to axons may continue after the primary injury and extend into the period of delayed cerebral ischaemia.^1,2,3,4Presence of secondary axonal degeneration in patients with SAH may be relevant to the outcome because, despite the high mortality (32–67%) during the hyperacute phase,^2,5 a considerable proportion of mostly young and otherwise healthy patients has the potential for good recovery from a limited degree of primary injury. In these patients, it is well known that secondary brain damage caused by delayed cerebral ischaemia adversely affects the potential for recovery.^2,3,4 About 50% of patients who survive do not return to their previous level of employment.^6,7,8In this longitudinal study, we monitored the development of axonal degeneration indirectly by measuring a biomarker for axonal degeneration (neurofilaments, reviewed by Petzold⁹). Firstly, we investigated whether neurofilaments would be increased early on (eg, a single peak, indicative of primary axonal injury) or rise late (eg, secondary peaks, suggestive of secondary axonal damage) in the disease course. Secondly, we tested whether the pattern of an anticipated¹ increase in neurofilament levels over time would be related to the degree of recovery.     

Unexplained syncope—is screening for carotid sinus hypersensitivity indicated in all patients aged >40?years?

Objective

To determine the frequency, age distribution and clinical presentation of carotid sinus hypersensitivity (CSH) among 373 patients (age range 15–92 years) referred to two autonomic referral centres during a 10‐year period.

Methods

Carotid sinus massage (CSM) was performed both supine and during 60° head‐up tilt. Beat‐to‐beat blood pressure, heart rate and a three‐lead electrocardiography were recorded continuously. CSH was classified as cardioinhibitory (asystole ⩾3 s), vasodepressor (systolic blood pressure fall ⩾50 mm Hg) or mixed. All patients additionally underwent autonomic screening tests for orthostatic hypotension and autonomic failure.

Results

CSH was observed in 13.7% of all patients. The diagnostic yield of CSM was nil in patients aged <50 years (n = 65), 2.4% in those aged 50–59 years (n = 82), 9.1% in those aged 60–69 years (n = 77), 20.7% in those aged 70–79 years (n = 92) and reached 40.4% in those >80 years (n = 57). Syncope was the leading clinical symptom in 62.8%. In 27.4% of patients falls without definite loss of consciousness was the main clinical symptom. Mild and mainly systolic orthostatic hypotension was recorded in 17.6%; evidence of sympathetic or parasympathetic dysfunction was found in none.

Conclusions

CSH was confirmed in patients >50 years, the incidence steeply increasing with age. The current European Society of Cardiology guidelines that recommend testing for CSH in all patients >40 years with syncope of unknown aetiology may need reconsideration. Orthostatic hypotension was noted in some patients with CSH, but evidence of sympathetic or parasympathetic failure was not found in any of them.Unexplained syncope is a common medical problem. In our series of 641 patients with recurrent syncope, a definite diagnosis could not be established in 28%, despite an extensive diagnostic investigation.¹ This is consistent with the literature, where figures range from 13% to 42% depending on populations studied and diagnostic algorithms used.²Carotid sinus hypersensitivity (CSH) refers to the occurrence of asystole ⩾3 s (cardioinhibitory CSH), a fall in systolic blood pressure of ⩾50 mm Hg (vasodepressor CSH) or both (mixed CSH), after carotid sinus massage (CSM). In patients with syncope of unknown origin and CSH on CSM, carotid sinus syndrome (CSS) is usually diagnosed, although the phenomenon of CSH has also been observed in up to 35% of asymptomatic older people in a recent study and there is no consistent definition of CSS in the literature.^3,4,5,6 To avoid confusion we will therefore refer to CSH instead of CSS throughout this paper, being well aware that the frequency of CSH may exceed that of CSS.CSH is a recognised cause of recurrent syncope and is increasingly recognised as accounting for unexplained falls in elderly people.^7,8 The diagnostic yield of CSM in patients >65 years presenting with syncope or unexplained falls was up to 45%, in studies by Kenny et al.^8,9,10 Subsequent studies that also included younger patients >50 or 60 years, however, have found lower prevalence rates of CSH, in the range of 17–21%.^11,12,13 Indeed, CSH was found to be rare in patients <50 years in a recent study by Puggioni et al,¹⁴ namely 4% in those aged <41 years and 11% in those aged 41–50 years.Despite these figures, the current European Society of Cardiology (ESC) guidelines still recommend testing for CSH in all patients >40 years who have unexplained syncope after basic evaluation consisting of history, physical examination including orthostatic blood pressure measurements and standard electrocardiography (ECG).^15,16 More data on the diagnostic yield of CSM in populations including patients <50 years of age are therefore needed to estimate the yield and thus cost effectiveness of these guidelines.In this study, we evaluated the results of CSM performed during a 10‐year period in two autonomic referral centres with an extensive regional and national patient‐referral base. We determined the frequency and clinical characteristics, especially the age distribution, of patients with CSH. Additionally, we analysed the detailed cardiovascular autonomic function tests of all patients with CSH, with an emphasis on the presence of orthostatic hypotension and evidence for autonomic failure, as it has been suggested that these coexist with CSH^7,8,17 and may cause or contribute to syncope.     

Profile of cognitive impairment in dementia associated with Parkinson's disease compared with Alzheimer's disease

Objective

To compare the profile of cognitive impairment in Alzheimer''s disease (AD) with dementia associated with Parkinson''s disease (PDD).

Methods

Neuropsychological assessment was performed in 488 patients with PDD and 488 patients with AD using the Mini‐Mental State Examination (MMSE) and the Alzheimer''s Disease Assessment Scale‐cognitive subscale (ADAS‐cog). Logistic regression analysis was used to investigate whether the diagnosis could be accurately predicted from the cognitive profile. Additionally, the cognitive profiles were compared with a normative group using standardised effect sizes (Cohen''s d).

Results

Diagnosis was predicted from the cognitive profile, with an overall accuracy of 74.7%. Poor performance of the AD patients on the orientation test in ADAS‐cog best discriminated between the groups, followed by poor performance of the PDD patients on the attentional task in MMSE. Both groups showed memory impairment, AD patients performing worse than PDD patients.

Conclusion

The cognitive profile in PDD differs significantly from that in AD. Performance on tests of orientation and attention are best in differentiating the groups.Alzheimer''s disease (AD) and Parkinson''s disease (PD) are the most common neurodegenerative diseases in the elderly. AD is primarily a dementing disease whereas PD is mainly characterised by a movement disorder. However, dementia is common among patients with PD (PDD), with an average point prevalence of 31%¹ and a cumulative prevalence close to 80%.² In PD, dementia is associated with rapid motor³ and functional decline,⁴ and increased mortality.⁵Cortical Lewy body pathology correlates best with dementia in PD^6,7,8,9; subcortical pathology¹⁰ and AD‐type pathology¹¹ have also been found to be associated with PDD. In addition to differences in morphological changes, AD and PDD also differ in the regional pattern of the pathology. In AD the first and most pronounced changes are found in the entorhinal cortex and parahippocampal region,¹² subsequently involving neocortical areas, including the posterior association cortices.¹³ In contrast, in patients with PD without dementia, brainstem nuclei and other subcortical structures are initially affected.¹⁴ In PDD, limbic areas, neocortical association cortices, and the motor cortex and primary sensory cortical areas are thought to be successively involved with disease progression.¹⁵Given the difference in the distribution and progression of pathology in AD and PDD, it is expected that their cognitive profiles would also differ.^16,17 AD is characterised by memory loss emerging in the early stages of the disease,¹⁸ primarily involving learning and encoding deficits¹⁹ which are associated with medial temporal lobe pathology.^20,21,22,23 As the disease progresses, deficits in language, praxis, visuospatial and executive functions gradually develop. In contrast, the cognitive deficits in the early stages of PDD are characterised by executive dysfunction, including impairment in attention²⁴ and working memory,^25,26,27 reflecting involvement of brainstem nuclei and frontal–subcortical circuits; deficits in visuoperceptual^28,29,30 and visuoconstructional tasks are also frequent.³¹ Memory impairment is often present^26,32,33,34 but whether it is primarily a consequence of frontally mediated executive deficits resulting in poor learning efficacy and retrieval, or whether involvement of limbic areas directly related to memory encoding (such as hippocampal atrophy) also contribute to memory impairment, is debated. Patients with PDD have difficulties in retrieving newly learned material, but perform better in recognition,³⁵ indicating that executive, rather than encoding, deficits, is the underlying mechanism. Conflicting results, however, have been reported recently^36,37 which could indicate that the type and mechanisms of memory deficits may vary within the PD group.³²Most studies investigating the cognitive profile of PDD patients included small samples which were not community based and thus not necessarily representative of the PD population at large. As there is evidence of interindividual heterogeneity,³³ such studies may not adequately reflect the cognitive profile of patients with PDD. In order to assess the profile of cognitive deficits in PDD compared with AD in larger patient populations, we analysed the baseline cognitive data from large clinical trials conducted with the cholinesterase inhibitor rivastigmine.^38,39     

Secondary motor disturbances in 101 patients with musician's dystonia

Objective

Musician''s focal dystonia is usually considered to be task specific but secondary motor disturbances have been reported also. We carried out a detailed evaluation of the incidence of these secondary motor problems in 101 patients.

Method

Symptoms were assessed using clinical histories, neurological examinations and observation of instrumental manoeuvres.

Results

53.5% of patients reported secondary motor disturbances in activities other than playing their main instrument, with the onset delayed in some cases by up to 12 years from the awareness of dystonic symptoms. 46.5% suffered from simple, 19.8% from complex and 33.7% from progressive cramps. Plucked string players (guitarists) mainly suffered from simple cramps while keyboardists more frequently displayed the progressive form. In all patients, symptoms were focal, and the type of cramp was unrelated to the severity of the perceived symptoms. Those patients playing a second instrument similar to their main instrument showed symptoms which worsened to a higher degree than those playing either only one instrument or whose second instrument was different.

Conclusions

Longer follow‐up assessments may reveal secondary motor symptoms that are not visible over shorter examination periods. Therefore, a thorough evaluation of everyday life motor activities should be considered in any clinical and treatment protocol. We speculate that the avoidance of movements that are similar to the main affected task may be of help in limiting symptoms. Consequently, focal dystonia may be considered more movement than task specific.The term occupational cramps is used to describe “a group of maladies in which certain symptoms are excited by the attempt to perform some often repeated muscular action, commonly one that is involved in the occupation of the sufferer”.¹ The term task specific dystonia is used to address the fact that one specific task and not other manual activities are affected. The best known focal dystonia is probably writer''s cramp, which inhibits the ability to write.² Dystonia has been diagnosed in, for example, surgeons, milkers, money counters, golfers, tennis and dart players and bowlers,^3,4,5 as well as in musicians.^6,7,8,9 Focal dystonia can manifest with a high degree of specificity, for example during longhand and not shorthand writing,³ or while playing classical but not electric guitar.¹⁰ Nevertheless, approximately 50% of writer''s cramp sufferers also report movement difficulties during other manual activities.^2,3,11 Such secondary motor problems have not been evaluated in detail in musicians, and reports focusing on the issue were based on small samples.Musicians achieve an exquisite level of motor performance, which is specific to the manual task they usually exercise, in agreement with reports on the neurophysiological basis of motor control of the hand.^{12,13,14,15,16,17,18} The reported percentages of secondary motor problems in affected musicians are usually low,^{7,8,9,19,20,21} but the heterogeneity of existing results does not allow one to draw satisfactory conclusions. Thus the question arises as to whether the per cent estimates reported previously are reliable, and what other factors may cause a bias towards the often used task specific characterisation of the disorder.We assessed the secondary motor problems reported by 101 musicians suffering from focal dystonia. The degree of specificity of the symptoms they reported, the type of secondary tasks being affected, as well as the characteristics they shared with the main affected tasks were inspected. Based on this, we discuss a possible explanation for the spreading of symptoms, and some aspects of relevance to prevent secondary motor effects.     

Generalised sensory system abnormalities in amyotrophic lateral sclerosis: a European multicentre study

Background

Amyotrophic lateral sclerosis (ALS) is defined as a disease of the motor neurones, although several studies indicate involvement of the sensory nervous system.

Aim

To evaluate the sensory nerve conduction studies (NCS) in 88 patients with ALS as part of a European multicentre study.

Methods

Seven European clinical neurophysiologists examined consecutive series of ALS patients. The examinations were peer reviewed, and the diagnosis of ALS was confirmed clinically.

Results

20 (22.7%) patients with ALS had sensory NCS abnormalities in at least one nerve. Of those, 11 (12.5% of all patients) obtained an additional peer review diagnosis of electrophysiological polyneuropathy. There was no difference between the subgroups of patients with normal versus abnormal sensory NCS findings with respect to age, duration and region of onset.

Conclusion

The findings support previous reports of sensory involvement in ALS, and raise the question of whether patients with ALS with sensory nerve abnormalities represent a variant of ALS. ALS associated with generalised sensory system abnormalities may be consistent with degeneration of motor neurones and dorsal root ganglion cells.Sporadic amyotrophic lateral sclerosis (ALS) is defined as a progressive degeneration of upper motor neurones (UMNs) and lower motor neurones (LMNs). Normal electrophysiological studies on sensory nerves are generally required for the diagnosis of ALS.¹ Nevertheless, several neurological, clinical neurophysiological and neuropathological studies have suggested that ALS is a more generalised neurodegenerative disorder.^{2,3,4,5,6,7,8,9,10,11,12,13,14,15,16}The aim of this study was to determine the incidence of patients with ALS with electrophysiological sensory nerve abnormalities and to examine the possible differences between patients with ALS with normal versus abnormal sensory nerve conduction studies (NCS). The study was carried out on the basis of electrodiagnostic examinations of 88 patients with ALS included in the European multicentre project ESTEEM (European Standardised Telematic tool to Evaluate Electrodiagnostic Methods).¹⁷     

Trunk performance after stroke: an eye catching predictor of functional outcome

Background and aim

Trunk performance is an important predictor of functional outcome after stroke. However, the percentage of explained variance varies considerably between studies. This may be explained by the stroke population examined, the different scales used to assess trunk performance and the time points used to measure outcome. The aim of this multicentre study was to examine the predictive validity of the Trunk Impairment Scale (TIS) and its subscales when predicting the Barthel Index score at 6 months after stroke.

Methods

A total of 102 subjects were recruited in three European rehabilitation centres. Participants were assessed on admission (median time since stroke onset 20 days) and 6 months after stroke. Correlation analysis and forward stepwise multiple regression analysis were used to model outcome.

Results

The best predictors of the Barthel Index scores at 6 months after stroke were total TIS score (partial R² = 0.52, p<.0001) and static sitting balance subscale score (partial R² = 0.50, p<.0001) on admission. The TIS score on admission and its static sitting balance subscale were stronger predictors of the Barthel Index score at 6 months than the Barthel Index score itself on admission.

Conclusions

This study emphasises the importance of trunk performance, especially static sitting balance, when predicting functional outcome after stroke. The TIS is recommended as a prediction instrument in the rehabilitation setting when considering the prognosis of stroke patients. Future studies should address the evolution of trunk performance over time and the evaluation of treatment interventions to improve trunk performance.Although the age specific incidence of major stroke has fallen over the past few years,¹ it is still the main cause of long term disability in adults, with a growing number of survivors being dependent for activities of daily living (ADL).^2,3 Frequently identified variables predicting ADL after stroke are age and initial severity of motor and functional deficits.⁴ Trunk performance has also been identified as an important independent predictor of ADL after stroke.^5,6,7,8,9 However, based on multiple regression analyses, the reported variance of functional outcome after stroke explained by trunk performance ranges from 9% to 71%.^5,6,7,8,9 Differences in reported variance could be explained by the stroke population included, the various scales used to measure trunk performance and the time points used to measure outcome.Previous studies evaluating the predictive validity of trunk performance after stroke were performed in a single rehabilitation setting, warranting caution when generalising results.^5,6,7,8,9,10 Clinical tools used to assess trunk performance are the Trunk Control Test,^5,6,10 trunk control items of the Postural Assessment Scale for Stroke patients^7,8 and trunk assessment of Fujiwara et al.⁹ A limitation of the first two tests is that they both have a ceiling effect, which makes their use less suitable in long term outcome studies.^5,11,12,13 Furthermore, the trunk control items of the Trunk Control Test and Postural Assessment Scale for Stroke patients are largely comparable with the items of the trunk measure of Fujiwara et al.⁹ All previously mentioned clinical tools include items in the supine position which involve rolling as well as only basic balance movements in sitting. Finally, with the exception of the trunk control items of the Postural Assessment Scale for Stroke patients,⁸ no study has evaluated the prognostic value of trunk performance when predicting functional outcome at 6 months after stroke.The Trunk Impairment Scale (TIS) for patients after stroke was designed to measure ADL related selective trunk movements rather than participation of the trunk in gross transfer movements.¹⁴ The TIS assesses static and dynamic sitting balance and trunk coordination. Reliability, validity, measurement error, internal consistency and discriminant ability of the TIS have been reported elsewhere.^14,15 The TIS has no ceiling effect in subacute and chronic stroke patients and already appeared to be strongly related to measures of gait, balance and functional ability in a cross sectional study.¹² To the best of our knowledge, the predictive value of the TIS and its subscales has not been evaluated. Including age and other measures of motor and functional performance could provide a useful combination of variables predicting outcome after stroke. The Barthel Index score is a widely accepted measure in stroke rehabilitation research and assesses functional milestones in stroke recovery. Predicting Barthel Index scores at 6 months after stroke based on measurements taken on admission to a rehabilitation centre would further establish the importance of trunk performance when predicting long term outcome after stroke. Experts in the field of neurological rehabilitation have addressed the trunk as the central key point of the body.¹⁶ Proximal stability of the trunk is a prerequisite for distal head and limb movement and therefore expected to be related to functional ADL.In summary, there is still a lack of clarity regarding the importance of trunk performance in functional outcome after stroke. Scales which have been used in previous studies have important statistical limitations and are likely to be a comprehensive measure of motor performance of the trunk. Therefore, the aim of this multicentre study was to examine the predictive validity of the TIS and its subcomponents, together with other known predictors, in predicting functional outcome measured as a Barthel Index score at 6 months after stroke.     

Symptomatic intracranial haemorrhage after intra-arterial thrombolysis in acute ischaemic stroke: assessment of 294 patients treated with urokinase

Background

The PROACT II trial showed that intra‐arterial thrombolysis (IAT) is effective for treatment of acute ischaemic stroke attributable to M1 and M2 segment occlusions. Incidence of symptomatic intracranial haemorrhage (sICH) was 10%.

Objective

: To evaluate the risk and predictors of sICH after IAT by using urokinase in a large number of patients presenting with the whole spectrum of cerebral vessel occlusions.

Methods

294 patients with stroke treated with intra‐arterial urokinase were retrospectively analysed. The risk of sICH as well as bleeding characteristics were assessed. Demographic and radiological data, time to treatment, urokinase dose, recanalisation rates, stroke aetiology and severity were analysed for predictors.

Results

sICH occurred in 14 of 294 (4.8%) patients. The median National Institute of Health Stroke Scale score of all patients was 15. All but one sICH were located in the infarcted brain tissue, and no sICH occurred in patients with peripheral vessel occlusions (M3 or M4 segments of the middle cerebral artery). Poor collaterals (p = 0.001), early signs of ischaemia on computed tomography (p = 0.003), higher urokinase dose (p = 0.019), lower recanalisation rate (p = 0.02) and higher diastolic blood pressure on admission (p = 0.04) were found to be correlated with sICH on univariate analysis. On multivariate analysis, poor collaterals (p = 0.004), urokinase dose (p = 0.021) and early signs on computed tomography (p = 0.026) remained predictors of sICH.

Conclusions

With regard to the whole spectrum of cerebral vessel occlusions, an incidence of <5% sICH after IAT is distinctly low. This result underlines the important role of IAT in the treatment of acute stroke.The aim of treatment in acute ischaemic stroke is revascularisation as fast as possible. For this purpose, both intravenous thrombolysis (IVT) and intra‐arterial thrombolysis (IAT) have proved to be effective.^1,2,3,4,5 The most devastating complication of both treatments is intracranial haemorrhage (ICH). ICH is categorised into haemorrhagic transformation, which is usually petechial and asymptomatic, and parenchymal haematomas without deterioration and those with clinical deterioration. Those with clinical deterioration are referred to as symptomatic ICH (sICH), which is associated with an increased mortality and occurs spontaneously in 0.6–4% of patients with ischaemic strokes. Thrombolysis increases the risk of sICH. Current literature reports wide ranges of incidence—for example, 3.3–21.2% for IVT and 0–14.3% for IAT.^{1,3,6,7,8,9,10,11,12,13,14}The largest IAT series was the PROACT II trial reporting on a defined subgroup of patients with stroke (n = 180) exclusively with M1 and M2 segment occlusions of the middle cerebral artery (MCA).³This study was conducted to evaluate the risk of sICH in the whole spectrum of patients with large cerebral artery occlusions treated with IAT. Characteristics of patients with sICH were assessed and predictors analysed.     

Myasthenia gravis: a long term follow-up study of Swedish patients with specific reference to thymic histology

Background

Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission. The majority of patients show abnormal thymic histology.

Setting

The study was performed at the Myasthenia Gravis Centre, Karolinska University Hospital, and at the Immunological Research Laboratory, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.

Patients and methods

Information was collected retrospectively from 1956 and prospectively from 1975 on clinical data, concomitant diseases, concentration of serum acetylcholine receptor antibodies (AChR‐abs), immunosuppressive treatment (IS) and response to it, in 537 patients of whom 326 were thymectomised. Follow‐up time was 1.5–50 years.

Results

Age at onset of MG increased from a median age of 24 years before 1975 to a median age of 61 years after 2000. Thymoma was found in 65, hyperplasia (HPL) in 185 and a normal thymus in 76 patients. The trans‐sternal surgical approach for thymectomy was used in 255 patients (78%). In five patients with thymoma, MG appeared after thymectomy. Of 537 patients, 466 (87%) had circulating AChR‐abs. IS was given to 300 (56%) patients, mostly those with thymoma (85%). In total, 441 patients (82%) showed an improvement. One‐third of patients with HPL, a quarter of those with thymoma, one‐fifth of those with a normal thymus and one‐seventh of those not operated on went into remission.

Conclusion

The prognosis for the majority of patients with MG is favourable, irrespective of thymic histology. The cause may be the use of immunomodulating therapy.Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission.^1,2 The prevalence of MG in Stockholm is 14.1 per 100 000 (17.1 for women and 10.8 for men).³The thymus gland plays a central role in the development of the T cell repertoire but its role in MG is not clear.^4,5,6 In MG, the thymic gland is normal in 15–20%, shows hyperplasia (HPL) in 65–75% and thymoma in 10–15% of patients.^1,4 HPL is characterised by lymphoid follicles with germinal centres containing mostly B lymphocytes.^4,5In 1892, Hoppe reported on a 40‐year‐old man with typical myasthenic bulbar fatigability who died of respiratory paralysis. At autopsy, a large mediastinal tumour was revealed.⁷ In 1944, Blalock described six MG patients without a thymoma, in whom thymectomy was of benefit.⁸ Thereafter, thymectomy has been an accepted therapy for MG. No controlled study of its efficacy has been published but a controlled study was planned in 2000, presented in 2003⁹ and has now started.Approximately 85% of patients with MG have circulating acetylcholine receptor antibodies (AChR‐abs) in serum.¹⁰ Of patients with pure ocular MG, about 30% are seronegative.Genetic factors contribute to the susceptibility of MG with HPL, but seem to be of minor importance in thymoma associated MG.^1,11The aim of this study was to describe the clinical characteristics, coexisting malignant, autoimmune and endocrine disorders, presence of AChR‐abs, use of immunosuppressive treatment (IS) and the response to it, in a population with MG with different thymic gland histology.