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.     

Stroke in patients with human immunodeficiency virus infection

Objective

To report the nature of stroke in patients infected with human immunodeficiency virus (HIV) in a region with high HIV seroprevalence and describe HIV associated vasculopathy.

Methods

Patients with first ever stroke, infected with HIV and prospectively included in the stroke register of the Groote Schuur Hospital/University of Cape Town stroke unit were identified and reviewed.

Results

Between 2000 and 2006, 67 of the 1087 (6,1%) stroke patients were HIV infected. Of these, 91% (n = 61) were younger than 46 years. Cerebral infarction occurred in 96% (n = 64) of the HIV positive patients and intracerebral haemorrhage in 4% (n = 3). HIV infected young stroke patients did not demonstrate hypertension, diabetes, hyperlipidaemia or smoking as significant risk factors for ischaemic stroke. Infection as a risk factor for stroke was significantly more common in HIV positive patients (p = 0.018, OR 6.4, CI 3.1 to 13.2). In 52 (81%) patients with ischaemic stroke, an aetiology was determined. Primary aetiologies comprised infectious meningitides/vasculitides in 18 (28%) patients, coagulopathy in 12 (19%) patients and cardioembolism in nine (14%) patients. Multiple aetiologies were present in seven (11%) patients with ischaemic stroke. HIV associated vasculopathy was identified in 13 (20%) patients. The HIV associated vasculopathy manifested either extracranially (seven patients) as total or significant carotid occlusion or intracranially (six patients) as medium vessel occlusion, with or without fusiform aneurysmal dilation, stenosis and vessel calibre variation.

Conclusion

Investigation of HIV infected patients presenting with stroke will determine an aetiology in the majority of patients. In our cohort, 20% of patients demonstrated evidence of an HIV associated vasculopathy.Infection with the human immunodeficiency virus (HIV) contributes to an increased risk of stroke.^1,2,3,4 In South Africa, 5.4 million people out of a total population of nearly 48 million South Africans are infected with HIV, giving a total prevalence of approximately 11% in 2006.⁵ Isolated reports have identified vasculopathy as a cause of stroke in HIV infected patients.^{6,7,8,9,10,11,12}We report the largest clinical cohort of HIV associated strokes prospectively admitted and investigated by the only tertiary stoke unit in Sub‐Saharan Africa. Groote Schuur Hospital is a university teaching hospital serving an open population of approximately 2.9 million persons. The selection bias of our Stroke Unit favours patients from low socioeconomic income groups (more affluent patients with health insurance tend to seek medical care in the private sector), young stroke patients under the age of 46 years (24% of the sample because of referral from other hospitals) and more severe strokes.Our objective was to describe the nature of stroke in HIV infected patients in clinical practice in a region with a high seroprevalence in the general population and further define HIV associated vasculopathy.     

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.     

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.     

Thrombolysis in patients older than 80 years with acute ischaemic stroke: Canadian Alteplase for Stroke Effectiveness Study

Background

The benefit of intravenous tissue plasminogen activator (tPA) given within 3 h of acute ischaemic stroke to patients over 80 years of age is uncertain.

Aim

To examine the clinical characteristics and complications and the predictors of outcome after intravenous tPA treatment in patients aged ⩾80 years.

Methods

Data (n = 1135) prospectively collected from the Canadian Alteplase for Stroke Effectiveness Study were reviewed and patients aged ⩾80 years (n = 270) treated with intravenous tPA for acute ischaemic stroke were compared with those aged <80 years (n = 865).

Results

The risk of symptomatic intracerebral haemorrhage did not differ between patients aged ⩾80 years and <80 years (4.4% (95% CI 2.3 to 7.6) v 4.6% (95% CI 3.3 to 6.2), p = 1.0). Favourable outcome, defined as a modified Rankin Score of 0–1 at 90 days, was seen in 26% of patients aged ⩾80 years and in 40% of those <80 (p<0.001). The following baseline characteristics were found to be more common in those aged ⩾80 years than in those aged <80 years: atrial fibrillation (37% v 18%; p<0.001); congestive heart failure (11% v 6%; p = 0.004); hypertension (59% v 48%; p = 0.002); and severity of stroke with a median National Institutes of Health Stroke Scale (NIHSS) score of 16 v 14 (p = 0.004). In the multivariable logistic regression analysis, age ⩾80 years, stroke severity, baseline Alberta Stroke Program Early CT Score and glucose level were found to be the major independent predictors of outcome.

Conclusion

In carefully selected elderly patients, the use of intravenous tPA was not found to be associated with an increased risk of symptomatic intracerebral haemorrhage. Age‐related differences were seen in the clinical characteristics and outcome in the elderly population.Thirty per cent of strokes occur in patients aged ⩾80 years but the role of intravenous thrombolysis in this age group is not well defined.¹ No randomised trials have focused specifically on elderly patients with acute ischaemic stroke. Recent studies analysed the risks and outcome of using intravenous tissue plasminogen activator (tPA) in elderly people and reported no increase in the risk of intracerebral haemorrhage, but the outcomes were not as favourable as in younger patients.^2,3 The number of patients studied, however, was very small, thereby preventing definitive conclusions from being drawn.People older than 80 years represent the fastest growing segment of the population in developed countries,⁴ and in view of the increased incidence of stroke with advancing age, stroke‐related disability is expected to increase.^5,6,7 We sought to examine the clinical characteristics, complications and predictors of outcome in patients aged ⩾80 years who were treated with intravenous tPA.     

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.     

Focal cortical dysplasia: long term seizure outcome after surgical treatment

Background

Studies of long term outcome after epilepsy surgery for cortical malformations are rare. In this study, we report our experience with surgical treatment and year to year long term outcome for a subgroup of patients with focal cortical dysplasia (FCD).

Methods

We retrospectively analysed the records of 49 patients (females n = 26; males n = 23; mean age 25 (11) years) with a mean duration of epilepsy of 18 years (range 1–45). Preoperative MRI, histological results based on the Palmini classification and clinical year to year follow‐up according to the International League Against Epilepsy (ILAE) classification were available in all patients.

Results

98% of patients had a lesion on preoperative MRI. In addition to lobectomy (n = 9) or lesionectomy (n = 40), 14 patients had multiple subpial transections of the eloquent cortex. The resected tissue was classified as FCD type II b in 41 cases with an extratemporal (88%) and FCD type II a in 8 cases with a temporal localisation (100%). After a mean follow‐up of 8.1 (4.5) years, 37 patients (76%) were seizure free, a subgroup of 23 patients (47%) had been completely seizure free since surgery (ILAE class 1a) and 4 patients (8%) had only auras (ILAE class 2). Over a 10 year follow‐up, the proportion of satisfactory outcomes decreased, mainly within the first 3 years. During long term follow‐up, 48% stopped antiepileptic drug treatment, 34% received a driver''s license and 57% found a job or training.

Conclusion

Surgical treatment of epilepsy with FCD is not only successful in the short term but also has a satisfying long term outcome which remains constant after 3 years of follow‐up but is not associated with better employment status or improvement in daily living.With the development of high resolution MRI in the past decade, cortical malformations have been detected more often in patients with drug resistant epilepsy.^1,2 Visualisation by MRI has aided diagnosis and surgical treatment of the largest group of cortical malformations (ie, the focal cortical dysplasias (FCDs)). Successful short term follow‐up with seizure free rates of 40–86% were described in several studies^{3,4,5,6,7,8,9} but only a few focused on long term outcome.^10,11,12 Most of these studies did not analyse subgroups of patients with the same histopathology, as other malformations or low grade gliomas were also included. The Engel classification,¹³ and not the newer International League Against Epilepsy (ILAE) classification,¹⁴ was used to describe the seizure outcome in all studies, and a year to year follow‐up, important for the long term course of these patients, was not included.The first aim of this study was a reclassification of all FCD cases according to the new Palmini classification¹⁵ to define a homogenous histopathological group. The second aim was to analyse the year to year long term outcome with respect to seizures according to the ILAE classification, antiepileptic drug (AED) use and socioeconomic outcome (eg, driving license and employment status).     

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.     

Clinical features of double infection with tick-borne encephalitis and Lyme borreliosis transmitted by tick bite

Background

In Latvia and other endemic regions, a single tick bite has the potential to transmit both tick‐borne encephalitis (TBE) and Lyme borreliosis.

Objective

To analyse both the clinical features and differential diagnosis of combined tick‐borne infection with TBE and Lyme borreliosis, in 51 patients with serological evidence, of whom 69% had tick bites.

Results

Biphasic fever suggestive of TBE occurred in 55% of the patients. Meningitis occurred in 92%, with painful radicular symptoms in 39%. Muscle weakness occurred in 41%; in 29% the flaccid paralysis was compatible with TBE. Only two patients presented with the bulbar palsy typical of TBE. Typical Lyme borreliosis facial palsy occurred in three patients. Typical TBE oculomotor disturbances occurred in two. Other features typical of Lyme borreliosis detected in our patients were distal peripheral neuropathy (n = 4), arthralgia (n = 9), local erythema 1–12 days after tick bite (n = 7) and erythema chronicum migrans (n = 1). Echocardiogram abnormalities occurred in 15.

Conclusions

Patients with double infection with TBE and Lyme borreliosis fell into three main clinical groups: febrile illness, 3 (6%); meningitis, 15 (30%); central or peripheral neurological deficit (meningoencephalitis, meningomyelitis, meningoradiculitis and polyradiculoneuritis), 33 (65%). Systemic features pointing to Lyme borreliosis were found in 25 patients (49%); immunoglobulin (Ig)M antibodies to borreliosis were present in 18 of them. The clinical occurrence of both Lyme borreliosis and TBE vary after exposure to tick bite, and the neurological manifestations of each disorder vary widely, with considerable overlap. This observational study provides no evidence that co‐infection produces unusual manifestations due to unpredicted interaction between the two diseases. Patients with tick exposure presenting with acute neurological symptoms in areas endemic for both Lyme borreliosis and TBE should be investigated for both conditions. The threshold for simultaneous treatment of both conditions should be low, given the possibility of co‐occurrence and the difficulty in ascribing individual neurological manifestations to one condition or the other.The Baltic region is an endemic focus for both tick‐borne encephalitis (TBE) and Lyme borreliosis transmitted by ticks.^1,2,3,4 In Latvia, 7061 cases of TBE and 3566 cases of Lyme borreliosis were registered between 1994 and 2003, out of a population of 2.4 million. Both tick species present in Latvia, Ixodes ricinus and persulcatus, can transmit the encephalitis virus, the borreliosis spirochete and more rarely erlichiosis. A single tick bite has the potential to transmit both infections.⁵ Despite their different clinical courses, TBE and Lyme borreliosis have neurological features in common: lymphocytic meningitis, flaccid or spastic limb weakness and cranial nerve involvement. Thus, differentiating between these disorders is important, given different approaches to treatment.Of the two infections, only TBE runs a biphasic course with the initial prodomal period of influenza‐like symptoms usually developing 1–2 weeks after the tick bite. Hence, after an asymptomatic period lasting 2–10 days, about a third of infected patients enter a second phase with aseptic meningitis.² Subsequently, 2–10% in Western TBE subtype or 10–25% in Eastern TBE subtype develop encephalitis, myelitis or meningoencephalomyelitis typically manifesting as combinations of flaccid paresis of the limbs, usually arms and neck, bulbar dysfunction, disorientation, aphasia and spastic paresis.^1,2 A poliomyelitis‐like syndrome is described in central European TBE.⁶ Manifestations of TBE in the Baltic may be heterogeneous, given that infection with the Western, Far Eastern and Siberian subtypes all cause human infection in Latvia.⁷ Although severe manifestations usually subside after 3–6 weeks, the convalescence period of TBE may be very long, with nearly 40% having a postencephalitic syndrome at 4 years.⁸ The uptake of TBE vaccination is increasing in the Baltic region.Classical Lyme borreliosis differs considerably from TBE and produces local and generalised forms, systemic involvement, and development over several stages. Its acute and chronic courses pose problems of diagnosis and management.^1,9 Diagnosis of neuroborreliosis requires a definite or possible tick bite, erythema migrans or seropositivity, and typical peripheral or central nervous system involvement.¹⁰ In early neuroborreliosis (2–10 weeks after tick bite) the most common neurological abnormalities are meningitis, meningoradiculoneuritis and cranial neuritis, particularly facial palsy.^1,9,10,11 Progressive chronic encephalomyelitis, polyneuritis and cerebrovascular disorders are later manifestations of Lyme borreliosis, usually occurring months after the initial infection. Neurological features are noted in 10–12% of all patients with Lyme borreliosis in Europe¹ and in 10–15% of patients in Northern America.¹¹ Neurological manifestations in 330 European patients with Lyme borreliosis included radicular pain (70%), headache (18%), peripheral paresis (45%), central paresis (4%), sensory disturbances (44%) and facial palsy (39%).¹ Borrelia infection takes a subclinical or minimally symptomatic course in up to 80% of the population after tick bites.¹² Importantly, borreliosis is treatable with antibiotics.TBE infection can be proven by specific and sensitive ELISA detection of antibody in cerebrospinal fluid (CSF), or by detection of genome through polymerase chain reaction.¹³ Serum IgM antibodies can remain positive for ⩾10 months.^2,14 By contrast, serological tests for Lyme borreliosis infection are less sensitive and specific to variable onset and occurrence of specific IgM and IgG antibodies, with recognised persistent seronegatives; direct detection of a pathogen is rarely possible, and reliance must be placed on interpreting the laboratory investigations in the light of the clinical picture.^13,15,16 Demonstration of intrathecal antibody production provides a specific test,¹⁷ but is not sensitive in detecting all forms of neuroborreliosis.¹⁵ Despite their different clinical courses, TBE and Lyme borreliosis have neurological features in common: lymphocytic meningitis, flaccid or spastic limb weakness, and cranial nerve involvement. Pain, particularly in a radicular distribution, and sensory disturbance are regarded as features more typical of Lyme borreliosis than TBE.Only limited information on double infection with TBE and Lyme borreliosis is available. Single cases, small series or serologically defined series with limited clinical information are described from Germany, Slovenia, Central Russia and Finland.^{18,19,20,21,22,23,24} This retrospective clinical observational study analyses the clinical features and problems of differential diagnosis in patients with evidence of both TBE and Lyme borreliosis infection in Latvia.     

Non-infectious fever in the neurological intensive care unit: incidence, causes and predictors

Background and objective

Non‐infectious causes of fever are often considered in critical neurological patients but their true significance has not been formally studied. The aim of this study was to evaluate the incidence, causes and predictors of fever in patients with acute neurological/neurosurgical disease and no documented infection.

Methods

Prospective data collection of consecutive patients admitted to the neurological intensive care unit (NICU) of an academic medical centre for more than 48 h was carried out. Fever was defined as body temperature ⩾101°F (38.3°C) documented on at least one measurement for 2 consecutive days. Patients were enrolled only if a diagnostic workup, including cultures of ⩾2 body samples, was performed before antibiotic use. Febrile patients with no proven evidence of infection were considered to have non‐infectious fever.

Results

93 patients were included in the final analysis. Fever was non‐infectious in 31 patients (33%). There were no differences between the infectious and non‐infectious fever groups in terms of age, use and duration of invasive catheters, daily duration of fever and number of days with fever. Documented infections tended to be more common among febrile patients with traumatic brain injury (52% vs 36%; p = 0.06). Non‐infectious fever was more frequent among patients with subarachnoid haemorrhage (48% vs 18%; p = 0.01) in whom it was associated with vasospasm (p = 0.03) and symptomatic vasospasm (p = 0.05). Non‐infectious fever started earlier (mean 2.6 vs 4 days; p = 0.007) and onset of fever within the first 72 h of admission predicted negative evaluation for infection (p = 0.01). Subarachnoid haemorrhage and fever onset within the first 72 h were independent predictors of non‐infectious fever on multivariable analysis.

Conclusions

Fever in the absence of documented infections occurs commonly in the NICU, especially among patients with subarachnoid haemorrhage and vasospasm. Early onset of fever predicts a non‐infectious cause.Between one‐quarter¹ and more than one‐half^2,3,4 of patients admitted to the neurological intensive care unit (NICU) develop fever. The cause of fever in these patients often remains unexplained. As hyperthermia is strongly detrimental for the recovery of the acutely injured brain^5,6,7,8,9 and contributes to an increase in the length of stay in the NICU,^4,10 timely and accurate diagnosis of the cause of fever in the NICU is crucial.Infections are the most common causes of fever in the NICU population but they are only documented in half of all febrile patients.¹ Central fever related to loss of the physiological regulation of body temperature by the hypothalamus is often proposed as a possible cause for persistent fever in acute neurological patients with no evidence of infection. There are no current means to confirm the diagnosis of central fever. Thus we can only assess its frequency by studying patients in whom fever remains unexplained after thorough investigations for infectious and other non‐infectious causes.The objective of this study was to determine the incidence, causes and predictors of non‐infectious fever in patients with acute neurological disease.     

Thrombolytic therapy for acute ischaemic stroke in octogenarians: selection by magnetic resonance imaging improves safety but does not improve outcome

Background

Owing to the fear of an increased bleeding risk, thrombolytic therapy is withheld from many patients with acute stroke >80 years of age.

Objective

To analyse the risk for symptomatic intracranial haemorrhage (sICH), morbidity and mortality after thrombolytic therapy in octogenarians focusing, in particular, on whether patients selected using magnetic resonance imaging (MRI) had a better risk:benefit ratio.

Methods

The prospectively collected single‐centre data of all patients treated with systemic thrombolytic therapy for acute ischaemic stroke since 1998 (n = 468) were reviewed, and patients ⩾80 years (n = 90) were compared with those aged <80 years (n = 378). In addition, the group of octogenarians was analysed with respect to initial imaging modality.

Results

The overall rate of sICH in the octogenarians was 6.9%, compared with 5.3% in younger patients (p = 0.61). In older patients selected by computed tomography, the rate of sICH was 9.4%; no patient selected by MRI had sICH (p = 0.10). Mortality in the octogenarians selected by computed tomography was 29.7% after 3 months as compared with 26.9% in the patients selected by MRI (p = 1.0). 20.3% of the octogenarians selected by computed tomography and 15.4% of those selected by MRI had a favourable outcome (modified Rankin scale ⩽1) after 3 months (p = 0.77).

Conclusion

Compared with younger patients, octogenarians do not have an increased risk of sICH. The use of MRI to select octogenarians for thrombolytic therapy seemed to decrease the risk of sICH, but did not influence the overall outcome after 3 months.The incidence of stroke increases steeply with age. In a population‐based survey, incidence of a first‐ever stroke was around 0.8 per 1000 population per year in people aged <75 years as compared with 14 per 1000 population per year in those aged 75–84 years and 29 per 1000 population per year in those aged >85 years.¹ With respect to changes in the population''s age structure in the industrialised world, the number of acute vascular events in elderly people will almost double in the course of the next 25 years.¹ Furthermore, age is an independent predictor for poor outcome after ischaemic stroke. Older patients, especially those aged >80 years, have a higher in‐hospital mortality risk and a favourable functional outcome is less likely.² Intravenous thrombolysis with recombinant tissue‐type plasminogen activator (rt‐PA) is the only approved therapy for patients with acute ischaemic stroke. However, the European and Australian rt‐PA stroke trials excluded patients >80 years of age.^3,4,5 Older patients were only allowed to be enrolled in the National Institute of Neurological Disorders and Stroke (NINDS) rt‐PA stroke study, but a mean age of 69 years in this trial shows that few patients >80 years of age were actually included.⁶ Owing to the lack of knowledge about the safety and efficacy of thrombolysis in this age group from randomised trials, the European Medicines Evaluation Agency (EMEA) recommends that rt‐PA not be used in patients with ischaemic stroke aged >80 years.⁷In the past few years, it has become increasingly popular to select patients for thrombolytic therapy using multiparametric magnetic resonance imaging (MRI) techniques. Our objective was to analyse the morbidity, mortality and risk for symptomatic intracranial haemorrhage (sICH) after thrombolytic therapy in octogenarians, focusing in particular on whether the risk:benefit ratio was higher in patients selected by MRI.     

Acute disseminated encephalomyelitis: a follow-up study in Taiwan

Background

Acute‐disseminated encephalomyelitis (ADEM) is a demyelinating disorder of the central nervous system, whose epidemiology, clinical presentations and functional outcome are incompletely understood in Asian populations.

Objective

To assess the clinical presentations, predisposing factors and functional outcome of ADEM in Taiwan.

Methods

50 patients initially diagnosed with ADEM (male, 19; female, 31) were enrolled from 1991 to 2005. Diagnosis of ADEM or multiple sclerosis was established during a follow‐up period of 2–120 months. 8 adult patients were noted to have taken the immunomodulatory drug, levamisole, within 3 months before onset of symptoms. The remaining 42 patients (male, 17; female, 25) were categorised by age as children (<16 years, n = 12), young adults (16–49 years, n = 21) and elderly adults (⩾50 years, n = 9). The clinical manifestations, predisposing factors and radiological findings were compared between different age groups and adult patients with or without levamisole use. Functional outcome was compared by a log‐rank test.

Results

Preceding upper respiratory tract infection was evident in 21 (50%) patients and only one young‐adult patient had received Rubella vaccine immunisation. The frequency of fever was higher in children (p = 0.04) and psychiatric symptoms were more prevalent in elderly patients (p = 0.03). Functional recovery was faster in children than in adults (p = 0.002). Initial Expanded Disability Status Scale score (odds ratio (OR) 1.9, p = 0.03) and no fever (OR 0.04, p = 0.06) were associated with poor outcome (modified Rankin scale ⩾2). After a mean (SD) follow‐up of 31.8 (9.9) months, 4 (9.5%) patients developed multiple sclerosis (3 (25%) children, 1 (4.7%) young adult, p = 0.03). The neurological disability, radiological and cerebrospinal fluid findings did not differ between patients with and without levamisole use. One elderly adult patient previously receiving levamisole developed multiple sclerosis of relapse‐remitting type after a mean follow‐up period of 36.9 months.

Conclusion

The clinical presentations, functional outcome and risk of developing multiple sclerosis differed between different age groups. Functional recovery was faster in children than in adults. Poor functional outcome was related to initial high Expanded Disability Status Scale score and absence of fever.Acute disseminated encephalomyelitis (ADEM) is a monophasic inflammatory demyelinating disorder of the central nervous system (CNS). Pathogenesis is suspected to be an autoimmune response to myelin, which is triggered by infection or immunisation via molecular mimicry.^1,2 Thus, ADEM may be the clinical counterpart to experimental allergic encephalomyelitis (EAE).³ The exact incidence is not known, but it was reported that the incidence of ADEM among persons aged <20 years residing in San Diego County, California was approximately 0.4/10⁵/year.⁴ More studies have been conducted in paediatric populations than in elderly adults and most reported series were Caucasians.^5,6,7,8 Few large series of ADEM have been published in Asian populations.⁹We thus assessed the precipitating factors, clinical presentations, cerebrospinal fluid (CSF) and radiological findings, and long‐term outcome in a cohort of ethnic Taiwanese patients with ADEM in different age groups, and attempted to determine the prognostic factors for poor functional outcome.     

Hippocampal volume and subcortical white matter lesions in late life depression: comparison of early and late onset depression

Background

Reduced hippocampal volume and increased prevalence of subcortical white matter lesions are associated with both recurrent early onset depression (EOD) and late onset depression (LOD). It is not clear whether these two factors differentially affect the age of onset of first depression. Therefore, we wished to investigate the relationship between age of first depression onset and hippocampal volume, with adjustment for subcortical white matter lesions.

Methods

MRI brain scans were used to compare hippocampal volumes and white matter lesions between age matched female patients (>60 years) with recurrent EOD and LOD and healthy controls.

Results

When comparing the three groups and adjusting for age, the Mini‐Mental State Examination score, total brain volume and total hippocampal volume were significantly smaller in patients with EOD compared with controls (5.6 vs 6.1 ml; p = 0.04). The prevalence of larger subcortical white matter lesions was higher in patients with LOD compared with patients with EOD (47% vs 8%; p = 0.002). Patients with LOD did not differ in hippocampal volume from patients with EOD or from controls.

Conclusions

In late life depression, age of first depression onset may distinguish between different independent neuropathological mechanisms. A small hippocampus volume may be a neuranatomical marker of EOD depression and larger subcortical white matter lesions could be an intermediate between cerebrovascular disease and LOD.Reduced hippocampal volume in late life depression (depression in those aged ⩾60 years) is associated with a chronic intermittent illness course.^1,2,3,4 Accordingly, older patients with recurrent early onset depression (EOD, first onset of depression before 60 years) would therefore have smaller hippocampal volumes compared with patients with late onset depression (LOD, first onset of depression at age 60 years or after) because of the longer duration of the disease. However, two recent studies showed smaller hippocampal volumes in patients with LOD compared with those with EOD.^5,6The latter observation could have been confounded by the increased prevalence of subcortical white matter lesions among patients with LOD^7,8,9 as these lesions may be related to hippocampal atrophy.^10,11,12 Therefore, in the current study we wished to investigate the relationship between age of onset of depression and hippocampal volume, with adjustment for subcortical white matter lesions, in elderly (⩾60 years) patients with chronic recurrent EOD and patients with LOD.     

Short-term efficacy of Epley's manoeuvre: a double-blind randomised trial

Background

Benign paroxysmal positional vertigo of the posterior canal (PC‐BPPV) is a common vestibular disorder and can be easily treated with Epley''s manoeuvre. Thus far, the short‐term efficacy of Epley''s manoeuvre for treatment of PC‐BPPV is unknown.

Objectives

To evaluate the efficacy of Epley''s manoeuvre for treatment of PC‐BPPV 24 h after applying the manoeuvre.

Methods

The short‐term efficacy of Epley''s manoeuvre was compared with a sham procedure in 66 patients with PC‐BPPV by using a double‐blind randomised study design.

Results

24 h after treatment, 28 of 35 (80%) patients in the Epley''s manoeuvre group had neither vertigo nor nystagmus on positional testing compared with 3 of 31 (10%) patients in the sham group (p<0.001).

Conclusion

Epley''s manoeuvre is shown to resolve PC‐BPPV both effectively and rapidly.Benign paroxysmal positional vertigo of the posterior canal (PC‐BPPV) is caused by dislodged otoconia trapped in the posterior semicircular canal that move under the influence of gravity after changes of head position in the plane of the canal. The resulting inappropriate endolymph flow activates hair cell receptors, causing positional vertigo and nystagmus.Epley''s manoeuvre is used to clear the affected semicircular canal from mobile particles by a set of five successive head positions that are hand guided by a therapist.¹ The efficacy of Epley''s manoeuvre for treatment of PC‐BPPV has been shown in numerous studies. A recent meta‐analysis identified seven randomised, controlled trials on Epley''s manoeuvre in clearly defined cases of PC‐BPPV that required the absence of nystagmus during positioning tests for a positive outcome. All studies showed higher remission rates in treated patients than in controls.² Outcome assessment, however, was blinded in only three of them.^3,4,5 Moreover, the magnitude of the effect of Epley''s manoeuvre has been questioned, as PC‐BPPV has the tendency to resolve spontaneously.⁶ So far, none of the trials on the efficacy of Epley''s manoeuvre has evaluated the short‐term efficacy in terms of hours as required for treatment assessment of spontaneously resolving disorders.     

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.     

Insular cortical ischaemia does not independently predict acute hypertension or hyperglycaemia within 3 h of onset

Objectives

To test the hypothesis that insular cortical ischaemia is associated with acute hypertension and hyperglycaemia.

Methods

From the Canadian Activase for Stroke Effectiveness Study, which included only patients treated with thrombolysis hyperacutely (ie, within 3 h of onset of stroke), 966 patients were identified with ischaemia affecting (n = 685), or sparing (n = 281), the insular cortex. Demographic and clinical data, pretreatment indices of blood pressure, blood glucose, atrial fibrillation, and clinical imaging and outcome measures were compared between the two groups. Multivariable linear regression was used to assess predictors of systolic blood pressure and glucose levels before thrombolysis.

Results

Pretreatment hypertension (p = 0.009), but not hyperglycaemia (p = 0.32), was predicted by insular ischaemia in univariable linear regression analyses. After adjusting for other factors, however, insular cortical ischaemia was not found to be an independent predictor for acute hypertension or hyperglycaemia.

Conclusions

Raised blood pressure or serum glucose levels in hyperacute (<3 h) cerebral ischaemia is not independently predicted by insular involvement. Several hours are required for sympathetic manifestations of insular ischaemia to evolve.Hypertension and hyperglycaemia are common manifestations of acute ischaemic stroke, affecting as many as 80% and 50% of patients, respectively, at the time of admission.¹ Although the aetiology of these changes is probably multifactorial, the insular cortex may have a role in the genesis of pathological sympathetic nervous system activation. Specific centres within the insula can alter blood pressure, heart rate and cardiac rhythm when stimulated,² transiently disabled with amobarbital,³ or lesioned experimentally.⁴ Patients with insular cortical infarcts subsequently have more frequent nocturnal rises in blood pressure, QT prolongations and cardiac arrhythmias, with concomitantly higher levels of norepinephrine compared with those with infarcts in other locations.⁵ Acute insular ischaemia, particularly right‐sided ischaemia, has been associated with higher systolic and diastolic blood pressures, heart rate and plasma catecholamine levels at admission and over the subsequent 5‐day period.⁶ Insular ischaemia may also be an independent predictor of acute stress hyperglycaemia.⁷ The timing of these changes is not entirely clear, as earlier investigations did not assess blood pressure and blood glucose levels hyperacutely (ie, <3 h from onset of stroke) in most patients.We assessed whether insular cortical ischaemia was a predictor of elevated blood pressure and blood glucose levels within the first 3 h after onset of stroke in a large prospective cohort of patients with stroke who were subsequently treated with intravenous thrombolysis.     

Essential tremor: predictors of disease progression in a clinical cohort

Objectives

To examine the utility of baseline factors to predict disease progression among a clinical cohort of patients diagnosed with essential tremor.

Measures

Tremor Rating Scale (TRS).

Methods

A clinical series of 128 consecutive patients diagnosed with essential tremor was included for study. 45 (35%) patients had at least one follow‐up exam (mean = 3.6 years). Baseline predictive factors examined included age, age at onset of symptoms, disease duration, sex, handedness, total tremor rating score, asymmetric tremor ratings, location of initial tremor onset, use of drugs for movement disorders, ETOH responsiveness of tremor, association of head or neck tremor, history of depression, familial history of essential tremor, Parkinson''s disease, Alzheimer''s disease and other movement disorders.

Results

On average, the TRS total score increased by <1 point per year before the first visit to the clinic and by about 2 points per year during the observed study period. The increase of 2 points per year during the observed study period represented an approximate 12% annual change from the mean TRS total score at the first clinic visit. Significant (p<0.05) predictive factors associated with increased tremor severity at the initial clinic visit included older age, longer disease duration, use of movement disorder drugs and the presence of voice tremor (r = 0.24, 0.27, 0.25, 0.19). The major factors associated with an increase in tremor severity from the initial clinic visit to the last follow up included asymmetrical tremor ratings, unilateral initial tremor onset and longer follow‐up duration (r = 0.32, 0.31, 0.30). Multivariate regression analysis accounted for about 17–30% of the variance in tremor ratings (p<0.05).

Conclusion

Essential tremor is a slow, progressive disease. The rate of disease progression and the factors associated with disease progression may vary throughout the disease course.Classically, essential tremor has been described as an action tremor (postural or kinetic)—that is, bilateral and midline, affecting the arms, head or voice with occasional involvement of the legs, chin and trunk. It is often accompanied by a family history of a similar tremor. Despite the progressive nature of the disease¹ and a high prevalence rate (about 3–6% of those over 40 years of age),^2,3 there are few prospective studies on essential tremor.^4,5,6 In brief, tremor amplitude tends to increase and progress more medially over time (7% per year)^4,5 and a larger proportion of women have head tremor throughout the disease course⁶; functional disability and psychological distress (71% and 43% of the sample) are common.⁵ The prognostic factors associated with disease progression have not been examined.     

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).     

A randomised controlled trial of a home based exercise programme to reduce the risk of falling among people with Parkinson's disease

Objective

To evaluate the effectiveness of a personalised home programme of exercises and strategies for repeat fallers with Parkinson''s disease (PD).

Method

Patients with a confirmed diagnosis of idiopathic PD, independently mobile, living at home in the community, experiencing more than one fall in the previous 12 months and with intact gross cognitive function were invited to participate in this randomised controlled trial. Usual care was compared with a personalised 6 week, home based exercise and strategy programme. The primary outcomes were rates of falling at 8 weeks and 6 months. Whether participants had repeat fallen, nearly fallen or experienced injurious falls were also examined. Functional Reach, the Berg Balance Test, PD Self‐assessment Scale and the Euro Quol were rated by a blinded assessor.

Results

Participants were randomised to the exercise (n = 70) and control (n = 72) groups. There was a consistent trend towards lower fall rates in the exercise group at both 8 weeks and 6 months and lower rates of injurious falls needing medical attention at 6 months. Lower rates of repeat near falling were evident for the exercise group at 8 weeks (p = 0.004) and 6 months (p = 0.007). There was a positive effect of exercises at 6 months on Functional Reach (p = 0.009) and quality of life (p = 0.033). No significant differences were found on other secondary outcomes measures.

Conclusion

There was a trend towards a reduction in fall events and injurious falls with a positive effect of exercises on near falls and quality of life.Postural instability and falls among people with Parkinson''s disease (PD) are common. In contrast with the estimated one‐third of the healthy population over 65 years who experience a fall,¹ two‐thirds of people living in the community with PD will have fallen in the previous 12 months² and those who have fallen two or more times in the previous year are likely to fall again in the next 3 months.³ As falls following PD can be injurious,⁴ prevention is important but postural instability is difficult to treat with medication. Physiotherapy may provide effective treatment for people with PD but two Cochrane reviews in 2001 on the general physical management of people with PD concluded there was insufficient evidence to support or refute the efficacy of physiotherapy or one form of physiotherapy over another for people with PD, and highlighted the need for more randomised controlled trials to test standard physiotherapy.^5,6 Most of the trials included in the systematic reviews recruited less than 20 subjects, and the use of poor research design and methodology was a common finding of the reviewers.Review of the literature on falls management among the general elderly population confirms that multidisciplinary fall prevention programmes can be beneficial for elderly people.^7,8 The most effective intervention was a multifactorial fall risk assessment and management programme. Exercise programmes, such as moderate intensity muscle strengthening and balance training, individually prescribed at home by a trained health professional, have been shown to be effective in reducing fall frequency among the elderly population living in the community.^7,8,9,10,11The purpose of this trial was to evaluate the effectiveness of a personalised home based exercise programme (activities selected from a menu of muscle strengthening, stretches, balance retraining and cognitive movement strategies for learning and compensating), administered by a physiotherapist for reducing fall events among people with PD. The research question addressed was: do repeat fallers with PD, who participate in an exercise programme of strength, balance training and strategies, experience fewer falls, near falls or injuries than those who do not?