Prevalence of cardiac right left shunts in migraine: a population-based case-control study.

We aimed to investigate the prevalence of cardiac right left shunts (RLS) in population-based samples of subjects with migraine with aura (n = 42), migraine without aura (n = 44) and controls without headache (n = 41). Cardiac RLS was assessed with transcranial Doppler sonography with intravenous injection of saline. Prevalence of RLS was highest in migraineurs with aura (45.2%) compared to migraineurs without aura (34.1%) and controls (41.5%). Permanent as opposed to latent RLS was more common among patients with migraine with aura (40.5%) than in patients with migraine without aura (23.3%) or controls (24.4%). Differences did not reach statistical significance between the three groups (p = 0.564 for RLS prevalence, p = 0.349 for prevalence of permanent shunts). Our data implicate a trend towards higher prevalence of RLS with larger shunts in subjects with migraine with aura.

No evidence of jugular venous valve insufficiency in patients with migraine--a controlled study.

BACKGROUND: Migraine with aura is associated with patent foramen ovale and right-left-shunt. Jugular venous valve insufficiency is a further vascular anomaly. It is a frequent finding in transient global amnesia which is associated with migraine. Therefore, we investigated the prevalence of jugular venous valve insufficiency in migraine. METHODS: Subjects included in this study were participants of the population based German Headache Study on the prevalence of primary headaches. In 36 patients with migraine with aura, 50 patients with migraine without aura and 43 controls without headaches duration of backward venous flow, peak velocity flow and diameters of the jugular venous valves were assessed by color-coded duplex and Doppler sonography and compared between groups. In all migraine patients, examination was performed between and not during migraine attacks. Therefore, 9 additional patients with chronic daily headache were investigated during headache. RESULTS: We did not find statistically significant differences in duration of flow, peak velocity flow and diameter of the jugular venous valves in patients with migraine with aura (mean values 0.53 ± 0.43 sec; 35.47 ± 33.87 cm/sec; 8.84 ± 3.17 mm), migraine without aura (0.61 ± 0.63 sec; 33.39 ± 25.80 cm/sec; 8.15 ± 3.02 mm) or controls (0.64 ± 0.51 sec; 35.28 ± 31.76 cm/sec; 8.79 ± 2.97 mm) (group effects p-values >0.41). For all parameters results were the same for the left and the right side of jugular venae (side effects p-values >0.09). Also patients with chronic daily migraine with headache during the examination showed no differences to controls (0.52 ± 0.49 sec; 27.95 ± 21,75 cm/sec; 8.07 ± 2.71 mm) (all p-values > 0.23). CONCLUSIONS: The prevalence of internal jugular venous valve insufficiency is not increased in persons with migraine.

Recovery of upper limb function after cerebellar stroke: lesion symptom mapping and arm kinematics.

BACKGROUND AND PURPOSE: Loss of movement coordination is the main postacute symptom after cerebellar infarction. Although the course of motor recovery has been described previously, detailed kinematic descriptions of acute stage ataxia are rare and no attempt has been made to link improvements in motor function to measures of neural recovery and lesion location. This study provides a comprehensive assessment of how lesion site and arm dysfunction are associated in the acute stage and outlines the course of upper limb motor recovery for the first 4 months after the infarction. METHODS: Sixteen adult patients with cerebellar stroke and 11 age-matched healthy controls participated. Kinematics of goal-directed and unconstrained finger-pointing movements were measured at the acute stage and in 2-week and 3-month follow-ups. MRI data were obtained for the acute and 3-month follow-up sessions. A voxel-based lesion map subtraction analysis was performed to examine the effect of ischemic lesion sites on kinematic performance. RESULTS: In the acute stage, nearly 70% of patients exhibited motor slowing with hand velocity and acceleration maxima below the range of the control group. MRI analysis revealed that in patients with impaired motor performance, lesions were more common in paravermal lobules IV/V and affected the deep cerebellar nuclei. Stroke affecting the superior cerebellar artery led to lower motor performance than infractions of the posterior cerebellar artery. By the 2-week-follow-up, hand kinematics had improved dramatically (gains in acceleration up to 86%). Improvements between the 2-week and the 3-month-follow-ups were less pronounced. CONCLUSIONS: In the acute stage, arm movements were mainly characterized by abnormal slowness (bradykinesia) and not dyscoordination (ataxia). The motor signs were associated with lesions in paravermal regions of lobules IV/V and the deep cerebellar nuclei. Motor recovery was fast, with the majority of gains in upper limb function occurring in the first 2 weeks after the acute phase.

Megalographia in children with cerebellar lesions and in children with attention-deficit/hyperactivity disorder.

Structural changes of the cerebellum have been reported in attention-deficit/hyperactivity disorder (ADHD) in several studies. The cerebellum is a structure essential for motor coordination and motor learning. Beside behavioral deficits, children with ADHD often show slight motor abnormalities. In the present study, handwriting was examined in both children with ADHD and children with cerebellar lesions. By writing the same sentence several times, letter height increased in the ADHD and cerebellar groups but not in controls. Comparable disorders of handwriting in cerebellar and ADHD children support previous studies, which suggest a contribution of cerebellar dysfunction to motor abnormalities in ADHD. However, an involvement of non-cerebellar dysfunctions in ADHD cannot be excluded.

Timing of conditioned eyeblink responses is impaired in children with attention-deficit/hyperactivity disorder.

Structural changes of the cerebellum have been reported in several psychiatric diseases like schizophrenia, autism and attention-deficit/hyperactivity disorder (ADHD). Beside behavioral deficits children with ADHD often show slight motor abnormalities. Cerebellar malfunction may contribute. The cerebellum is a structure essential for motor coordination, various forms of motor learning and timing of motor responses. In the present study, eyeblink conditioning was applied to investigate learning and timing of motor responses both in children with ADHD and children with cerebellar lesions. Acquisition, timing and extinction of conditioned eyeblink responses were investigated in children with ADHD, children with chronic surgical cerebellar lesions and controls using a standard delay paradigm with two different interstimulus intervals. Timing of conditioned eyeblink responses was significantly impaired in children with ADHD in the long interstimulus interval condition. Also in children with cerebellar lesions conditioned responses (CR) tended to occur earlier than in controls. Incidences of CRs were significantly reduced in children with cerebellar lesions and tended to be less in children with ADHD than in controls. Extinction of the CRs was impaired in children with cerebellar lesions in both interstimulus interval conditions and in children with ADHD in the long interstimulus interval condition. Cerebellar malfunction may contribute to disordered eyeblink conditioning in ADHD. However, because CR abnormalities differed between ADHD and cerebellar subjects, dysfunction of non-cerebellar structures cannot be excluded.

Timing of conditioned eyeblink responses is impaired in cerebellar patients.

In the present study, timing of conditioned eyeblink responses (CRs) was investigated in cerebellar patients and age-matched controls using a standard delay paradigm. Findings were compared with previously published data of CR incidences in the same patient population (Gerwig et al., 2003; Timmann et al., 2005). Sixteen patients with pure cortical cerebellar degeneration (spinocerebellar ataxia type 6 and idiopathic cerebellar ataxia), 14 patients with lesions within the territory of the superior cerebellar artery, and 13 patients with infarctions within the territory of the posterior inferior cerebellar artery were included. The affected cerebellar lobules and possible involvement of cerebellar nuclei were determined by three-dimensional magnetic resonance imaging (MRI) in patients with focal lesions (n = 27). Based on a voxel-by-voxel analysis, MRI lesion data were related to eyeblink conditioning data. CR incidence was significantly reduced, and CRs occurred significantly earlier in patients with cortical cerebellar degeneration and lesions of the superior cerebellum compared with controls. Incidence and timing of CRs was not impaired in patients with lesions restricted to the posterior and inferior cerebellum. Voxel-based MRI analysis revealed that cortical areas within the anterior lobe (Larsell lobule HV) were most significantly related to timing deficits, whereas reduced CR incidences were related to more caudal parts (lobule HVI) of the superior cerebellar cortex. The present data suggest that different parts of the superior cerebellar cortex may be involved in the formation of the stimulus association and appropriate timing of conditioned eyeblink responses in humans. Extracerebellar premotoneuronal disinhibition, however, is another possible explanation for changes in CR timing.

Involvement of the human cerebellum in short-term and long-term habituation of the acoustic startle response: a serial PET study.

OBJECTIVE: Numerous studies have shown an involvement of the human cerebellum in motor learning, but little is known about the role of the cerebellum in learning of unspecific aversive reactions. The present study sought to distinguish which areas of the human cerebellum and brain-stem are involved in short-term habituation (STH) and long-term habituation (LTH) of the acoustic startle response. METHODS: On 5 consecutive days 42 acoustic startle stimuli were applied each day in 8 male healthy subjects. On the first and on the fifth day of the experiment [15O]H2O PET scans were performed. RESULTS: Electromyographic recordings revealed a significant decrease of the startle response within each day (STH) and across the 5 days of the experiment (LTH). On both days a decrease of regional cerebral blood flow (rCBF) across PET scans was found in the medial cerebellum most probably reflecting reduced sensory feedback during STH. Between days an increase of rCBF in the dorsomedial pons, in the mesencephalon and in an area of the medial cerebellum was observed. These activations may reflect increased inhibition of the startle response during LTH and correspond to previous animal lesion studies. Furthermore, during LTH an increase of rCBF within the lateral cerebellum in lobule HVI/Crus I was detected. CONCLUSIONS: These results suggest that distinct parts of the medial and lateral cerebellum are involved in habituation of the acoustic startle response. Lobule HVI/Crus I most likely plays a more general role in implicit learning processes considering its involvement in several conditioning paradigms. SIGNIFICANCE: The results of the present study contribute to the understanding of cerebellar involvement in learning of unspecific aversive reactions.

Extinction of conditioned eyeblink responses in patients with cerebellar disorders.

Extinction of conditioned eyeblink responses (CRs) was analyzed in sixteen patients with pure cortical cerebellar degeneration, 14 patients with lesions within the territory of the superior cerebellar artery (SCA), 13 patients with infarctions within the territory of the posterior inferior cerebellar artery (PICA) and 45 age-matched controls. Three-dimensional (3D) magnetic resonance (MRI) data sets were acquired in patients with focal lesions to identify affected cerebellar lobules and possible involvement of nuclei. Eyeblink conditioning was performed using a standard delay protocol. At the end of the experiment 10 CS-alone trials were presented as extinction trials. Controls showed significant effects of extinction that is a significant decline comparing CR-incidences in the extinction trials and the last block of 10 trials of the paired trials. In the group of all cerebellar patients, however, no significant effects of extinction were observed. In patients with unilateral lesions effects of extinction were present on the unaffected, but not on the affected side. Deficits of extinction were observed in PICA and SCA patients both with and without involvement of cerebellar nuclei. Extending previous reports in cerebellar patients the present findings show that the ipsilateral cerebellar hemisphere contributes to extinction of conditioned eyeblink responses in humans. It cannot be ruled out, however, that impaired acquisition affected the extinction results.

Cerebellar involvement in verb generation: an fMRI study.

A possible role of the human cerebellum in the generation of verbs corresponding to presented nouns has been suggested. Previous functional brain imaging studies have compared generation of verbs with the reading of nouns as a measure of verb generation. In the present fMRI study involving healthy human subjects, the effects of speech articulation and motor imagery associated with verb production were investigated in greater detail. Generation of verbs to visually presented nouns was compared to a condition in which subjects read those same verbs that had been individually generated by each subject. Activation in lobule HVI/Crus I of the right cerebellar hemisphere was found as a measure of verb generation. In contrast, reading of verbs as a measure of speech articulation evoked cerebellar activations in both left and right paravermal lobule VI. These results suggest an involvement of the right lateral cerebellar hemisphere in linguistic functions during verb generation. Alternatively, effects of inner speech could also possibly explain the results.

Strategies in detection of the primary tumour in anti-Yo associated paraneoplastic cerebellar degeneration.

In patients with anti-Yo associated paraneoplastic cerebellar degeneration (PCD) neurological symptoms precede the diagnosis of the underlying cancer in about 60%. Ovarian carcinoma, breast cancer and other gynaecological malignancies are most frequently found as causative malignancies. Antitumour treatment should be applied in an early stage of disease. The identification of the tumour is a diagnostic challenge in many of these patients. In the first of two patients reported here a pelvic tumour was suggested after detection of a pathological lymph node and elevated tumour markers. The intraoperative findings appeared macroscopically normal during ovariectomy with adnexectomy. Not until microscopic examination of the resected tissue was performed was a tubal adenocarcinoma found. If intrapelvic gynaecological tumours are suspected a deliberate surgical exploration seems to be justified, but only after an intensive diagnostic investigation. To search for the underlying cancer in patients with paraneoplastic neurological disorders successive CT and [18F]-FDG-PET are widely recommended. Instead of this in the second reported patient whole-body dual-modality PET/CT was performed revealing enhanced uptake in three regions of the left thorax. By combining function and anatomy PET/CT was able to localise the lesions and characterise them as lymph node metastases of breast cancer. Diagnosis could be confirmed by subsequently executed needle biopsy. PET/CT seems to be highly applicable in the investigation of paraneoplastic disorders with unknown primary cancer. It may help in guidance of needle biopsy or to optimise the results of deliberate surgery and it provides whole-body tumour staging in a single session with higher diagnostic accuracy than PET alone.

Long-term outcome of vertigo and dizziness associated disorders following treatment in specialized tertiary care: the Dizziness and Vertigo Registry (DiVeR) Study.

To investigate the long-term outcome of interdisciplinary treatment in a tertiary care neuro-otology institution after 2 years as part of the Dizziness and Vertigo Registry study. Risk factors associated with unfavourable outcome were assessed. 3113 consecutive patients with disorders of vertigo and dizziness were recruited prospectively between March 2010 and February 2012. Patients were clinically assessed and treated according to their diagnosis. Standardized instruments were used at baseline and at 2-year follow-up [Dizziness Handicap Inventory (DHI), Quality of Life Questionnaire, General Depression Scale, Stait-Trait Anxiety Index], as well as a custom health-related questionnaire. The primary outcome variable of this observational study was the change in DHI after 2 years. Patients suffered from phobic postural vertigo (23%), benign peripheral paroxysmal vertigo (14.4%), unilateral vestibulopathy (10.5%), central vestibular disorders (8%), Menière's disease (9.8%), vestibular migraine (6.9%), bilateral vestibulopathy (5.5%), and vestibular paroxysmia (3.1%). Mean disease duration was 4.6 ± 6.3 years. 1272 patients were available for follow-up, 1159 completed the DHI score. 72.1% of patients improved in DHI score from baseline to 2 years follow-up. Mean reduction in DHI score was 14 points (p = 0.02). Long-term outcome following diagnosis and treatment in a specialized tertiary care centre is good and persistent after 2 years. Risk factors for an unfavourable outcome were advanced age, severe disability, constant vertigo or dizziness, and concomitant back pain, while depression and anxiety did not contribute to this risk considerably.

Involvement of the human cerebellum in fear-conditioned potentiation of the acoustic startle response: a PET study.

Fear-conditioned potentiation of the startle response was used to study the role of the cerebellum in associative learning of non-specific aversive reactions in healthy human subjects using PET. Prior PET scanning initially neutral light stimuli were paired with painful electric shocks (fear-conditioning phase). Four PET-scans each were performed with presentation of acoustic startle stimuli (T), fear-conditioned light stimuli (L) or acoustic stimuli paired with light (LT, potentation phase). As a measure of fear-conditioning subtraction of condition T from LT revealed an increase of regional cerebellar blood flow (rCBF) in the left cerebellar hemisphere. Subtraction of condition L from LT, as a measure of fear-conditioned potentiation, revealed an increase of rCBF in the medial cerebellum. Different parts of the cerebellum appear to be involved in this form of motor associative learning.

Functional recovery and rehabilitation of postural impairment and gait ataxia in patients with acute cerebellar stroke.

Studies about recovery from cerebellar stroke are rare. The present study assessed motor deficits in the acute phase after isolated cerebellar stroke focusing on postural impairment and gait ataxia and outlines the role of lesion site on motor outcome, the course of recovery and the effect of treadmill training. 23 patients with acute and isolated cerebellar infarction participated. Deficits were quantified by ataxia scores and dynamic posturography in the acute phase and in a follow up after 2 weeks and 3 months. MRI data were obtained to correlate lesion site with motor performance. Half of the patients that gave informed consent and walked independently underwent a 2-week treadmill training with increasing velocity. In the acute phase patients showed a mild to severe ataxia with a worse performance in patients with infarction of the superior in comparison to the posterior inferior cerebellar artery. However, after 3 months differences between vascular territories were no longer significant. MRI data showed that patients with larger infarct volumes had a significantly more severe ataxia. In patients with ataxia of stance, gait and lower limbs lesions were more common in cerebellar lobules IV to VI. After 3 months a mild ataxia in lower limbs and gait, especially in gait speed persisted. Because postural impairment had fully recovered, remaining gait ataxia was likely related to incoordination of lower limbs. Treadmill training did not show significant effects. Future studies are needed to investigate whether intensive coordinative training is of benefit in patients with cerebellar stroke.

Pallidal deep brain stimulation relieves camptocormia in primary dystonia.

Camptocormia, characterised by a forward flexion of the thoracolumbar spine may occur in various movement disorders, mainly in Parkinson's disease or in primary dystonia. In severe cases, patients with camptocormia are unable to walk. While treatment options are limited, deep brain stimulation (DBS) with bilateral stimulation of the subthalamic nucleus or globus pallidus internus (GPi) has been proposed as a therapeutic option in refractory cases of Parkinson's disease. Here we present two patients with severe camptocormia as an isolated form of dystonia and as part of generalised dystonia, respectively, which were both treated with bilateral stimulation of the GPi. Symptoms of dystonia were assessed using the Burke-Fahn-Marsden dystonia rating scale (BFM) before and during deep brain stimulation. In both patients there was a significant functional improvement following long-term bilateral GPi stimulation and both patients gained ability to walk. In the first patient with an isolated dystonic camptocormia the BFM motor subscore for the truncal flexion improved by 75 %. The total BFM motor score in the second patient with a camptocormia in generalised dystonia improved by 45 %, while the BFM score for truncal flexion improved by 87 %. In both patients the effect of the bilateral GPi stimulation on camptocormia was substantial, independent of generalisation of dystonia. Therefore, GPi DBS is a possible treatment option for this rare disease.

Posterior reversible encephalopathy syndrome (PRES): electroencephalographic findings and seizure patterns.

To better describe seizure type, frequency, and electroencephalographic (EEG) findings in posterior reversible encephalopathy syndrome (PRES) and correlate these data with clinical and magnetic resonance imaging (MRI) data, we retrospectively assessed medical charts and EEG studies of patients with PRES treated between 2004 and 2011. Data collected included patients' underlying pathology, lesion distribution by MRI, seizure type and frequency, EEG pathologic background activity, focal pathology, and epileptogenic activity. Thirty-eight of 49 adults with PRES suffered from seizures; 17 underwent EEG and were included in the analysis. Perpetuating factors were similar to those reported in the literature. In 15 of 17 patients, MRI showed widespread involvement rather than purely occipital lesions. Nine patients had subcortical and cortical involvement. Seizures were single short grand mal (GM) in 11, serial GM in 2, recurrent GM in 2, and additional focal seizures in 2. No seizures were noted beyond the first day. After discontinuation of antiepileptic medication, no patients experienced seizure recurrence during 6-month follow-up. EEG showed diffuse theta/delta slowing in 13 patients and epileptogenic activity with focal sharp-wave and periodic lateralizing epileptiform discharges in 2 patients. Seizures in PRES are most commonly single GM and are usually of limited duration. EEG shows variable theta/delta slowing. Focal EEG pathology is seen in patients with focal seizures. Seizures occur early after disease onset and terminate spontaneously or under therapy during the first 24 h. Seizure recurrence beyond 24 h and chronic epilepsy were not seen. Seizures in PRES are frequent but appear to be uncomplicated and do not herald worse prognosis. EEG is helpful in evaluating the degree of encephalopathy and monitoring epileptic activity. Long-term antiepileptic medication does not appear to be warranted.

Evaluation of multiple-session delay eyeblink conditioning comparing patients with focal cerebellar lesions and cerebellar degeneration.

The acquisition and timing of delay-conditioned eyeblink responses (CRs) have been shown to be significantly impaired in patients with disorders restricted to the cortex of the superior cerebellum. We were interested if patients improve incidences and timing of CRs across three sessions on three consecutive days. A standard delay paradigm was used in 9 patients with diffuse cerebellar degeneration, 13 patients with ischemic cortical cerebellar lesions and in 13 controls. High-resolution magnetic resonance imaging (MR imaging) was used to ensure that hemispheral lobules VI and/ or Crus I were lesioned in all stroke patients with the interposed nuclei being preserved. On day 1 patients with stroke but not with degenerative disorders showed significant CR acquisition, although total CR incidences remained significantly lower than in controls. No further improvement was visible on days 2 and 3 neither in patients with focal lesions nor in patients with cerebellar degeneration. CRs occurred earlier in cerebellar patients, most pronounced in patients with degenerative disorders. In patients with stroke but not in the degenerative group timing had improved on the third day close to values of the control subjects. Findings show that lesions of the cerebellar cortex produce permanent deficits in the acquisition of delay-conditioned eyeblink responses. Overall, mean CR incidence was higher in focal compared to degenerative disorders, most likely because the critical lobules (VI and Crus I) were lesioned only in part. Intact anterior lobe, which it thought to contribute to CR timing, may explain recovery of disordered timing in focal cerebellar patients.

Postural and gait performance in children with attention deficit/hyperactivity disorder.

Up to 50% of children and adolescents with attention deficit/hyperactivity disorder (ADHD) exhibit motor abnormalities including altered balance. Results from brain imaging studies indicate that these balance deficits could be of cerebellar origin as ADHD children may show atrophy in those regions of the cerebellum associated with gait and balance control. To address this question, this study investigated postural and gait abilities in ADHD children and compared their static and dynamic balance with children with known lesions in the cerebellum. Children diagnosed with ADHD according to DSM IV-TR diagnostic criteria were compared with children with chronic surgical cerebellar lesions and age-matched controls. A movement coordination test was used to assess differences in motor development. Postural and gait abilities were assessed using posturography, treadmill walking and a paced stepping task. Volumes of the cerebellum and the cerebrum were assessed on the basis of 3D magnetic resonance images (MRI). Children with cerebellar lesions showed significant performance decrements in all tasks compared with the controls, particularly in the movement coordination test and paced stepping task. During dynamic posturography ADHD-participants showed mild balance problems which correlated with findings in cerebellar children. ADHD children showed abnormalities in a backward walking task and minor abnormalities in the paced stepping test. They did not differ in treadmill walking from the controls. These findings support the notion that cerebellar dysfunction may contribute to the postural deficits seen in ADHD children. However, the observed abnormalities were minor. It needs to be examined whether balance problems become more pronounced in ADHD children exhibiting more prominent signs of clumsiness.

Reliability and validity of ICARS in focal cerebellar lesions.

To evaluate the therapies for cerebellar diseases appropriate neurological assessment methods to measure severity of ataxia are required. Reliability and validity of the semiquantitative International Cooperative Ataxia Rating Scale (ICARS) has recently been examined in patients with degenerative ataxias. We evaluated reliability (internal consistency), criterion-related validity and internal construct validity of ICARS for the first time in patients with focal cerebellar lesions (68 patients with surgical lesions and 68 patients with ischemic lesions). For comparison 45 patients with degenerative cerebellar ataxia were included. We found an excellent Cronbach's alpha as a measurement for internal consistency which was independent from underlying disease. Criterion-related validity was high. Total ICARS score mirrored clearly the immediate postsurgical worsening and the improvement during the first 3 months after focal surgical and ischemic lesions, whereas in chronic state of focal and degenerative cerebellar disorders ICARS score remained nearly unchanged. Principal component analysis in patients with focal lesions revealed five distinct and clinically meaningful factors which corresponded to the four ICARS subscores and reflected the laterality of kinetic functions. In degenerative disorders, however, the items for the subscore "kinetic function" loaded to more than one factor. Total ICARS score seems to be a useful and valid measurement to describe the time course of ataxia in patients with focal and degenerative disorders affecting primarily the cerebellum. Validity of subscores however is good in focal, but not in degenerative disorders.