Is there evidence of bradykinesia in essential tremor?

BACKGROUND AND PURPOSE: Essential tremor (ET) is a movement disorder primarily characterized by upper limb postural and kinetic tremor. Although still under-investigated, bradykinesia may be part of the phenotypic spectrum of ET. The aim was to evaluate bradykinesia features in ET through clinical examination and kinematic analysis of repetitive finger movements. Data collected in ET patients were compared with those recorded in Parkinson's disease patients and healthy controls. METHODS: Overall, 258 subjects participated in the study (90 ET patients, 84 Parkinson's disease patients and 84 healthy controls). Repetitive finger tapping was kinematically recorded using a motion analysis system. Movement velocity, amplitude and decrement (sequence effect) were measured. The three groups were first compared by one-way analysis of variance. A cluster analysis was also performed to better address the data variability observed in ET patients. Possible relationships between kinematic and clinical data were assessed in ET patients. RESULTS: Essential tremor patients were slower than healthy controls. Movement slowness in ET did not correlate with postural or kinetic tremor severity. It was also found that movement slowness in ET was not associated with a sequence effect, which instead is a common feature in Parkinson's disease. Cluster analysis showed that a proportion of ET patients may have movement abnormalities similar to those observed in Parkinson's disease. CONCLUSIONS: Movement slowness without sequence effect is a common feature in ET patients. The present findings are relevant when interpreted in the context of the new tremor classification system and in the development of a more accurate bradykinesia definition.

Disease progression in blepharospasm: a 5-year longitudinal study.

BACKGROUND AND PURPOSE: The clinical manifestation of dystonic spasms in blepharospasm (BSP) patients may be heterogeneous. Whether the varying phenomenology of eyelid spasms becomes manifest sequentially during the course of the disease or aggregates in separate clusters according to different disease courses is still unclear. For this purpose, the clinical features in BSP patients were evaluated longitudinally over a 5-year period and also the blink reflex recovery cycle was tested in a subgroup of BSP patients. METHODS: Sixty BSP patients were videotaped at time 0 and after approximately 5 years of follow-up. Two experts in movement disorders, who were blinded to the video order, reviewed the videotapes and scored the severity of BSP using the Blepharospasm Severity Rating Scale. Changes in the R2 recovery index were also evaluated in 18 patients twice, i.e. upon enrolment and at the follow-up. RESULTS: The severity of BSP worsened significantly over the 5-year follow-up period owing to the appearance or the increased duration and frequency of prolonged spasms. It was also found that the blink reflex recovery cycle worsened at follow-up in comparison with the baseline. CONCLUSIONS: This study shows that the disease progression of BSP is characterized by the appearance or worsening of prolonged spasms. Prolonged spasms are accompanied by changes in the excitability of brainstem interneurons. Aging-related effects may exacerbate the pathophysiological mechanisms underlying spasms.

Corticobasal syndrome: neuroimaging and neurophysiological advances.

Corticobasal degeneration (CBD) is a neurodegenerative condition characterized by 4R tau protein deposition in several brain regions that clinically manifests itself as a heterogeneous atypical parkinsonism typically expressed in adulthood. The prototypical clinical phenotype of CBD is corticobasal syndrome (CBS). Important insights into the pathophysiological mechanisms underlying motor and higher cortical symptoms in CBS have been gained by using advanced neuroimaging and neurophysiological techniques. Structural and functional neuroimaging studies often show asymmetric cortical and subcortical abnormalities, mainly involving perirolandic and parietal regions and basal ganglia structures. Neurophysiological investigations including electroencephalography and somatosensory evoked potentials provide useful information on the origin of myoclonus and on cortical sensory loss. Transcranial magnetic stimulation demonstrates heterogeneous and asymmetric changes in the excitability and plasticity of primary motor cortex and abnormal hemispheric connectivity. Neuroimaging and neurophysiological abnormalities in multiple brain areas reflect asymmetric neurodegeneration, leading to asymmetric motor and higher cortical symptoms in CBS.

Tremor in motor neuron disease may be central rather than peripheral in origin.

BACKGROUND AND PURPOSE: Motor neuron disease (MND) refers to a spectrum of degenerative diseases affecting motor neurons. Recent clinical and post-mortem observations have revealed considerable variability in the phenotype. Rhythmic involuntary oscillations of the hands during action, resembling tremor, can occur in MND, but their pathophysiology has not yet been investigated. METHODS: A total of 120 consecutive patients with MND were screened for tremor. Twelve patients with action tremor and no other movement disorders were found. Ten took part in the study. Tremor was recorded bilaterally using surface electromyography (EMG) and triaxial accelerometer, with and without a variable weight load. Power spectra of rectified EMG and accelerometric signal were calculated. To investigate a possible cerebellar involvement, eyeblink classic conditioning was performed in five patients. RESULTS: Action tremor was present in about 10% of our population. All patients showed distal postural tremor of low amplitude and constant frequency, bilateral with a small degree of asymmetry. Two also showed simple kinetic tremor. A peak at the EMG and accelerometric recordings ranging from 4 to 12 Hz was found in all patients. Loading did not change peak frequency in either the electromyographic or accelerometric power spectra. Compared with healthy volunteers, patients had a smaller number of conditioned responses during eyeblink classic conditioning. CONCLUSIONS: Our data suggest that patients with MND can present with action tremor of a central origin, possibly due to a cerebellar dysfunction. This evidence supports the novel idea of MND as a multisystem neurodegenerative disease and that action tremor can be part of this condition.

Re-emergent tremor in Parkinson's disease: the effect of dopaminergic treatment.

BACKGROUND AND PURPOSE: Patients with Parkinson's disease (PD) with resting tremor may be affected by a tremor that appears after a varying latency while a posture is maintained, a phenomenon referred to as re-emergent tremor (RET). The aim of the study was to evaluate the occurrence and clinical features of RET in patients with PD tested off and on treatment, and to compare the effect of dopaminergic treatment on RET with the effect on resting and action tremor. METHODS: We consecutively enrolled 100 patients with PD. Patients were clinically evaluated 24 h after withdrawal of therapy (off-treatment phase) and 60 min after therapy administration (on-treatment phase). We collected the demographic and clinical data of patients with PD. The severity of the disease was assessed by means of the Hoehn and Yahr scale and Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale part III. We evaluated the latency, severity and body side affected both off and on treatment in patients with RET. RESULTS: Re-emergent tremor was present in 24% of the patients with PD off treatment and in 19% of the patients on treatment. Dopaminergic treatment reduced the clinical severity of RET. Dopaminergic treatment increased the number of patients with unilateral RET and reduced the number of those who had bilateral RET. RET and resting tremor responded similarly to dopaminergic treatment, whereas action tremor was less responsive. Patients with RET had milder motor symptoms than patients without RET both off and on treatment. CONCLUSIONS: Dopaminergic treatment modified RET occurrence, severity and body distribution. Dopaminergic depletion plays a role in the pathophysiology of RET.

Pain in Parkinson's disease: facts and uncertainties.

Pain is one of the most common and troublesome non-motor symptoms of Parkinson's disease (PD). It can appear at any time during the disease and is often present before diagnosis. However, there is little or no consensus on its definition. An expert group of clinicians with relevant research experience met to review the existing evidence and to identify gaps in our understanding leading towards AUTHOR: 'understanding towards' has been changed to 'understanding leading towards'. Please check and confirm that this is appropriate an optimized therapy of pain in PD. Key findings from epidemiologic, neurophysiologic, neuroimaging and clinical studies are reviewed. In each case, the evidence base is limited by wide variations in the definitions of pain applied, study methodologies and populations evaluated. Disease-related and medical conditions trigger spontaneous pain in patients with PD, which is then abnormally processed and results in painful manifestations in specific body parts. Dopaminergic medications, such as rotigotine, as well as opiate analgesics, such as oxycodone, have shown positive results but future studies with more detailed pain characterization at inclusion are warranted.

Spread of dystonia in patients with idiopathic adult-onset laryngeal dystonia.

BACKGROUND AND PURPOSE: Adult-onset laryngeal dystonia (LD) can be isolated or can be associated with dystonia in other body parts. Combined forms can be segmental at the onset or can result from dystonia spread to or from the larynx. The aim of this study was to identify the main clinical and demographic features of adult-onset idiopathic LD in an Italian population with special focus on dystonia spread. METHODS: Data were obtained from the Italian Dystonia Registry (IDR) produced by 37 Italian institutions. Clinical and demographic data of 71 patients with idiopathic adult-onset LD were extracted from a pool of 1131 subjects included in the IDR. RESULTS: Fifty of 71 patients presented a laryngeal focal onset; the remaining subjects had onset in other body regions and later laryngeal spread. The two groups did not show significant differences of demographic features. 32% of patients with laryngeal onset reported spread to contiguous body regions afterwards and in most cases (12 of 16 subjects) dystonia started to spread within 1 year from the onset. LD patients who remained focal and those who had dystonia spread did not show other differences. CONCLUSIONS: Data from IDR show that dystonic patients with focal laryngeal onset will present spread in almost one-third of cases. Spread from the larynx occurs early and is directed to contiguous body regions showing similarities with clinical progression of blepharospasm. This study gives a new accurate description of LD phenomenology that may contribute to improving the comprehension of dystonia pathophysiology.

Correction to: The Italian Dystonia Registry: rationale, design and preliminary findings.

In the original article, Gina Ferrazzano was affiliated to Department of Neurology and Psychiatry, Neuromed Institute IRCCS, Sapienza University of Rome, Pozzilli, Italy.The corrected affiliation should be: Neuromed Institute IRCCS, Pozzilli, IS, Italy.

Relationship between pain and motor and non-motor symptoms in Parkinson's disease.

BACKGROUND AND PURPOSE: Although female gender, depressive symptoms and medical conditions predisposing to pain are more common in patients with Parkinson's disease (PD) with pain, no study has yet explored the relationship between pain and other non-motor symptoms (NMS). METHODS: A total of 321 consecutive patients with PD [190 men/131 women aged 68.3 (SD 9.2) years] attending four Italian movement disorder clinics were studied. Demographic/clinical data were obtained by a standardized interview and the NMS scale. The association of pain with motor and NMS was assessed by multivariable logistic regression models. RESULTS: At the time of the study, 180 patients with PD (56%) reported chronic pain that, in most cases, was described as being muscular or arthralgic pain. Pain preceded the onset of motor signs in 36/180 patients. In the main-effect model, factors independently associated with pain were female sex [odds ratio (OR), 2.1; P = 0.01], medical conditions predisposing to pain (OR, 2.9; P < 0.001), Hoehn-Yahr staging (OR, 1.9; P = 0.04), motor complications (OR, 4.7; P = 0.04) and NMS belonging to the sleep/fatigue (OR, 1.6; P = 0.04) and mood/cognition (OR, 1.6; P = 0.03) domains. Most explanatory variables in the multivariable analysis were similarly distributed in patients in whom pain may have been related to PD or to a cause other than PD. CONCLUSIONS: We confirm that pain in PD is more frequent in women and in subjects with medical conditions predisposing to painful symptoms. Moreover, this strengthens the association between pain and motor severity measures and NMS domains, particularly sleep and mood disturbances.

BDNF and LTP-/LTD-like plasticity of the primary motor cortex in Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome (GTS) is characterized by motor and vocal tics and often associated with obsessive-compulsive disorder (OCD). Responses to intermittent/continuous theta-burst stimulation (iTBS/cTBS), which probe long-term potentiation (LTP)-/depression (LTD)-like plasticity in the primary motor cortex (M1), are reduced in GTS. ITBS-/cTBS-induced M1 plasticity can be affected by brain-derived neurotrophic factor (BDNF) polymorphism. We investigated whether the BDNF polymorphism influences iTBS-/cTBS-induced LTP-/LTD-like M1 plasticity in 50 GTS patients and in 50 age- and sex-matched healthy subjects. In GTS patients, motor and psychiatric (OCD) symptom severity was rated using the Yale Global Tic Severity Scale (YGTSS) and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). We compared M1 iTBS-/cTBS-induced plasticity in healthy subjects and in patients with GTS. We also compared responses to TBS according to BDNF polymorphism (Val/Val vs Met carriers) in patients and controls. Fourteen healthy subjects and 13 GTS patients were Met carriers. When considering the whole group of controls, as expected, iTBS increased whereas cTBS decreased MEPs. Differently, iTBS/cTBS failed to induce LTP-/LTD-like plasticity in patients with GTS. When comparing responses to TBS according to BDNF polymorphism, in healthy subjects, Met carriers showed reduced MEP changes compared with Val/Val individuals. Conversely, in patients with GTS, responses to iTBS/cTBS were comparable in Val/Val individuals and Met carriers. YGTSS and Y-BOCS scores were comparable in Met carriers and in Val/Val subjects. We conclude that iTBS and cTBS failed to induce LTP-/LTD-like plasticity in patients with GTS, and this was not affected by BDNF genotype.

The Italian Dystonia Registry: rationale, design and preliminary findings.

The Italian Dystonia Registry is a multicenter data collection system that will prospectively assess the phenomenology and natural history of adult-onset dystonia and will serve as a basis for future etiological, pathophysiological and therapeutic studies. In the first 6 months of activity, 20 movement disorders Italian centres have adhered to the registry and 664 patients have been recruited. Baseline historical information from this cohort provides the first general overview of adult-onset dystonia in Italy. The cohort was characterized by a lower education level than the Italian population, and most patients were employed as artisans, builders, farmers, or unskilled workers. The clinical features of our sample confirmed the peculiar characteristics of adult-onset dystonia, i.e. gender preference, peak age at onset in the sixth decade, predominance of cervical dystonia and blepharospasm over the other focal dystonias, and a tendency to spread to adjacent body parts, The sample also confirmed the association between eye symptoms and blepharospasm, whereas no clear association emerged between extracranial injury and dystonia in a body site. Adult-onset dystonia patients and the Italian population shared similar burden of arterial hypertension, type 2 diabetes, coronary heart disease, dyslipidemia, and hypothyroidism, while hyperthyroidism was more frequent in the dystonia population. Geographic stratification of the study population yielded no major difference in the most clinical and phenomenological features of dystonia. Analysis of baseline information from recruited patients indicates that the Italian Dystonia Registry may be a useful tool to capture the real world clinical practice of physicians that visit dystonia patients.

Rest tremor in idiopathic adult-onset dystonia.

BACKGROUND: Tremor in dystonia has been described as a postural or kinetic abnormality. In recent series, however, patients with idiopathic adult-onset dystonia also displayed rest tremor. METHODS: The frequency and distribution of rest tremor were studied in a cohort of 173 consecutive Italian patients affected by various forms of idiopathic adult-onset dystonia attending our movement disorder clinic over 8 months. RESULTS: Examination revealed tremor in 59/173 patients (34%): 12 patients had head tremor, 34 patients had arm tremor, whilst 13 patients presented tremor in both sites. Head tremor was postural in all patients, whereas arm tremor was postural/kinetic in 28 patients, only at rest in one and both postural/kinetic and at rest in 18 patients. Patients with tremor were more likely to have segmental/multifocal dystonia. Patients who had rest tremor (either alone or associated with action tremor) had a higher age at dystonia onset and a greater frequency of dystonic arm involvement than patients with action tremor alone or without tremor. CONCLUSIONS: Both action and rest tremor are part of the tremor spectrum of adult-onset dystonia and are more frequently encountered in segmental/multifocal dystonia. The higher age at dystonia onset and the greater frequency of arm dystonia in patients with rest tremor may have pathophysiological implications and may account, at least in part, for the previous lack of identification of rest tremor as one possible type of tremor present in dystonia.

Early visuomotor integration processes induce LTP/LTD-like plasticity in the human motor cortex.

To investigate whether visuomotor integration processes induce long-term potentiation (LTP) and depression (LTD)-like plasticity in the primary motor cortex (M1), we designed a new paired associative stimulation (PAS) protocol coupling left primary visual area (V1) activation achieved by hemifield visual evoked potentials (VEPs) and transcranial magnetic stimulation (TMS) over the left M1, at specific interstimulus intervals (ISIs), delivered at 1 Hz (V-PAS). Before and after V-PAS, we measured motor evoked potentials (MEPs). To clarify the mechanisms underlying V-PAS, we tested the effect of 1-Hz repetitive TMS (rTMS), 0.25-Hz V-PAS and rTMS, and a shorter 0.25-Hz V-PAS protocol. To examine V-PAS with contralateral V1 activation, we delivered V-PAS activating the right V1. To clarify whether V-PAS increases V1 activity or parieto- and premotor-to-M1 connectivity, before and after V-PAS, we examined VEPs and MEPs evoked by paired-pulse techniques. V-PAS increased, decreased, or left MEPs unchanged according to the ISI used. After 1-Hz rTMS MEPs decreased. Although 0.25-Hz rTMS elicited no aftereffect, 0.25-Hz V-PAS modulated MEPs according to the ISI used. The short 0.25-Hz V-PAS protocol left MEPs unchanged. Contralateral V-PAS inhibited MEPs. After V-PAS, VEPs remained unchanged and the premotor-to-M1 inhibitory connections decreased. V-PAS induces M1 LTP/LTD-like plasticity by activating premotor-to-motor connections.

Abnormal motor cortex excitability during linguistic tasks in adductor-type spasmodic dysphonia.

In healthy subjects (HS), transcranial magnetic stimulation (TMS) applied during 'linguistic' tasks discloses excitability changes in the dominant hemisphere primary motor cortex (M1). We investigated 'linguistic' task-related cortical excitability modulation in patients with adductor-type spasmodic dysphonia (ASD), a speech-related focal dystonia. We studied 10 ASD patients and 10 HS. Speech examination included voice cepstral analysis. We investigated the dominant/non-dominant M1 excitability at baseline, during 'linguistic' (reading aloud/silent reading/producing simple phonation) and 'non-linguistic' tasks (looking at non-letter strings/producing oral movements). Motor evoked potentials (MEPs) were recorded from the contralateral hand muscles. We measured the cortical silent period (CSP) length and tested MEPs in HS and patients performing the 'linguistic' tasks with different voice intensities. We also examined MEPs in HS and ASD during hand-related 'action-verb' observation. Patients were studied under and not-under botulinum neurotoxin-type A (BoNT-A). In HS, TMS over the dominant M1 elicited larger MEPs during 'reading aloud' than during the other 'linguistic'/'non-linguistic' tasks. Conversely, in ASD, TMS over the dominant M1 elicited increased-amplitude MEPs during 'reading aloud' and 'syllabic phonation' tasks. CSP length was shorter in ASD than in HS and remained unchanged in both groups performing 'linguistic'/'non-linguistic' tasks. In HS and ASD, 'linguistic' task-related excitability changes were present regardless of the different voice intensities. During hand-related 'action-verb' observation, MEPs decreased in HS, whereas in ASD they increased. In ASD, BoNT-A improved speech, as demonstrated by cepstral analysis and restored the TMS abnormalities. ASD reflects dominant hemisphere excitability changes related to 'linguistic' tasks; BoNT-A returns these excitability changes to normal.

Heat-evoked experimental pain induces long-term potentiation-like plasticity in human primary motor cortex.

We designed a new paired associative stimulation (PAS) protocol that combines experimental pain evoked by laser stimuli and transcranial magnetic stimulation (TMS) (Laser-PAS) to primary motor cortex (M1). We tested in healthy subjects whether Laser-PAS elicits cortical plasticity as reflected by long-term changes in motor-evoked potentials (MEPs) (after-effects). In separate experiments, we examined numerous variables including changes induced by varying the interstimulus intervals (ISIs) and Laser-PAS-induced changes in target and non-target muscle MEPs. We measured MEPs after repetitive laser or TMS (rTMS) pulses, and compared magnetic- and electric (TES)-induced MEPs. We tested MEPs after applying Laser-PAS with laser pulses ipsilaterally to M1. Finally, we studied subjects receiving an N-methyl-D-aspartate (NMDA) receptor antagonist (memantine) or placebo (α-lipoic acid). During Laser-PAS at the 50 ms ISI MEPs decreased, thereafter they increased for 60 min; other ISIs induced no after-effects. The after-effects remained restricted to the target muscle. Repetitive laser pulses and rTMS induced no after-effects. After Laser-PAS, TMS-induced MEPs increased, whereas TES-induced MEPs did not. Laser-PAS with laser pulses ipsilaterally to M1 left MEPs unchanged. Memantine, but not α-lipoic acid, abolished the after-effects. In conclusion, Laser-PAS elicits NMDA-dependent cortical plasticity and provides new insights into human pain-motor integration.

Understanding the role of cerebellum in early Parkinson's disease: a structural and functional MRI study.

Increasing evidence suggests that the cerebellum may have a role in the pathophysiology of Parkinson's disease (PD). Hence, the scope of this study was to investigate whether there are structural and functional alterations of the cerebellum and whether they correlate with motor and non-motor symptoms in early PD patients. Seventy-six patients with early PD and thirty-one age and sex-matched healthy subjects (HS) were enrolled and underwent a 3 T magnetic resonance imaging (MRI) protocol. The following MRI analyses were performed: (1) volumes of 5 cerebellar regions of interest (sensorimotor and cognitive cerebellum, dentate, interposed, and fastigial nuclei); (2) microstructural integrity of the cerebellar white matter connections (inferior, middle, and superior cerebellar peduncles); (3) functional connectivity at rest of the 5 regions of interest already described in point 1 with the rest of brain. Compared to controls, early PD patients showed a significant decrease in gray matter volume of the dentate, interposed and fastigial nuclei, bilaterally. They also showed abnormal, bilateral white matter microstructural integrity in all 3 cerebellar peduncles. Functional connectivity of the 5 cerebellar regions of interest with several areas in the midbrain, basal ganglia and cerebral cortex was altered. Finally, there was a positive correlation between abnormal functional connectivity of the fastigial nucleus with the volume of the nucleus itself and a negative correlation with axial symptoms severity. Our results showed that structural and functional alterations of the cerebellum are present in PD patients and these changes contribute to the pathophysiology of PD in the early phase.

How pain arises in Parkinson's disease?

In recent years, increasing attention has centred on pain in Parkinson's disease (PD). Pain in PD is heterogeneous in quality and body distribution. To clarify how the various pain types relate to PD and to propose plausible treatment strategies, in this paper we reviewed psychophysical, neurophysiological and imaging data reported in parkinsonian patients with and without pain. Most available evidence supports abnormal central nociceptive input processing that probably reflects an impairment in the lateral and medial pain pathways. Changes in central pain processing probably underlie all the different pain types and also intervene in patients with PD without pain. Thus, altered pain processing might predispose patients with PD to spontaneous pain that is variable in quality. These background pain-processing abnormalities may interact with additional factors (such as contractures secondary to marked rigidity/bradykinesia, dystonia and medical conditions associated with painful symptoms), thus causing pain to manifest itself clinically in various ways and providing candidate targets for pain treatment in PD.

Somatosensory temporal discrimination threshold may help to differentiate patients with multiple system atrophy from patients with Parkinson's disease.

BACKGROUND AND PURPOSE: Somatosensory temporal discrimination threshold (STDT) is defined as the threshold at which two tactile stimuli applied to the skin are perceived as clearly distinct. The aim of the study was to investigate whether the extent of STDT alterations differs between patients with parkinsonian type multiple system atrophy (MSA-P) and patients with Parkinson's disease (PD). Possible differences between the two groups may help to differentiate MSA-P from PD. METHODS: STDT was investigated in 20 patients with MSA-P, 21 patients with PD and 18 age-matched healthy subjects. The clinical evaluation included the Mini-Mental State Examination, Hoehn and Yahr Scale, Frontal Assessment Battery, Unified Multiple System Atrophy Rating Scale for patients with MSA-P, and Unified Parkinson's Disease Rating Scale for patients with PD. STDT was investigated by delivering paired electrical stimuli starting with an inter-stimulus interval (ISI) of 0 ms (simultaneous pair), and progressively increasing the ISIs in 10-ms steps. RESULTS: Between-group anova showed that STDT statistically differed in MSA-P versus patients with PD and healthy subjects. Post hoc showed that STDT values in patients with MSA-P were significantly higher than those in patients with PD and healthy subjects. Receiver operating characteristic curve analysis showed that STDT testing yielded high diagnostic specificity and sensitivity. CONCLUSIONS: STDT is abnormal in patients with MSA-P and PD. The degree of STDT abnormalities is higher in patients with MSA-P than in patients with PD.

Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson's disease.

OBJECTIVE: To summarize the 2010 EFNS/MDS-ES evidence-based treatment recommendations for the management of Parkinson's disease (PD). This summary includes the treatment recommendations for early and late PD. METHODS: For the 2010 publication, a literature search was undertaken for articles published up to September 2009. For this summary, an additional literature search was undertaken up to December 2010. Classification of scientific evidence and the rating of recommendations were made according to the EFNS guidance. In cases where there was insufficient scientific evidence, a consensus statement ('good practice point') is made. RESULTS AND CONCLUSIONS: For each clinical indication, a list of therapeutic interventions is provided, including classification of evidence.