Resetting of orthostatic tremor associated with cerebellar cortical atrophy by transcranial magnetic stimulation.

OBJECTIVES: To investigate the resetting effects of transcranial magnetic stimulation over motor cortex on orthostatic tremor, characterized by high-frequency electromyographic discharges in weight-bearing muscles, particularly orthostatic tremor (OT) associated with cerebellar cortical atrophy; and to compare our results with those obtained in primary OT, for which transcranial magnetic stimulation does not reset tremor. DESIGN: Study of 3 patients who clinically exhibited a sporadic pancerebellar syndrome associated with isolated cerebellar atrophy and features of OT. SETTING: Research hospital. MAIN OUTCOME MEASURES: Electromyograms and transcranial magnetic stimulation studies with a resetting index calculated on the basis of the timing of measured bursts and predicted bursts for a magnetic stimulus given at increasing delays. RESULTS: Surface electromyographic recordings in weight-bearing muscles showed tremor with a frequency of 14, 15, and 14 Hz in the 3 patients. Transcranial magnetic stimulus was able to reset OT. Resetting index was 0.72. CONCLUSIONS: Transcranial magnetic stimulus resets OT associated with cerebellar cortical atrophy, emphasizing the role of motor cortex in the genesis of OT associated with a cerebellar dysfunction. Our results argue in favor of a distinct pathophysiological mechanism of primary OT and OT associated with cerebellar cortical atrophy.

Rhythmic cortical and muscle discharges induced by fatigue in corticobasal degeneration.

We describe a patient presenting clinical features of corticobasal degeneration (CBD), including reflex myoclonus in the left upper limb. This patient complained of a marked worsening of involuntary movements in the left upper limb after exercise. We analysed the electrophysiological characteristics of myoclonus in the basal state and after a fatiguing exercise in the left upper limb. In the basal condition, single trials recording EEG showed a cortical complex occurring 20 ms after stimulation of the left median nerve. Surface EMG recordings of the left first dorsal interosseous (FDI) revealed an isolated biphasic C1 response 49 ms after stimulation. After exercise, single trials recording EEG following shocks to the left median nerve showed rhythmic complexes with a duration of approximately 80 ms. EEG complexes were made of a series of 3 bursts, with intervals between bursts tending to cluster at approximately 22 ms. These rhythmic complexes were associated with repetitive activity in the left FDI. We conclude that rhythmic cortical and muscle discharges can be induced by fatigue in CBD.

Shift from hypermetria to hypometria in an aberrant recovery following cerebellar infarction.

Cerebellar hypermetria, a classical sign designating the overshoot when the patient attempts to reach rapidly an aimed target, is associated with an imbalance between timing and/or intensity of agonist and antagonist EMG activities. Recovery of hypermetria following a cerebellar ischemia or hemorrhage has been demonstrated to take place in a multistage process, but aberrant recovery following a cerebellar stroke has not been described previously. We report an 85-year-old woman presenting an abnormal recovery following a cerebellar infarction. We identified three successive stages. At stage 1, fast wrist flexion movements were severely hypermetric and associated with three EMG defects: a delayed onset latency of antagonist EMG activity, a reduction of intensity of the agonist EMG activity and a depression of intensity of antagonist EMG activity. At stage 2, movements were characterized by terminal oscillations around the target and the onset latency of the antagonist activity had returned to normal. At stage 3, movements were markedly hypometric, the intensity of the antagonist EMG activity had returned to normal, while the intensity of the agonist EMG activity remained abnormally low. This case illustrates an abnormal reprogramming of the EMG triphasic pattern, resulting in the shift from severe hypermetria to severe hypometria.

Different types of cerebellar hypometria associated with a distinct topography of the lesion in cerebellum.

We recorded ballistic wrist flexion movements in fifteen cerebellar patients exhibiting hypometria. The movement and the associated agonist and antagonist EMG activities were analysed. On the basis of the topography of the cerebellar lesion, our patients were divided into three groups. In the first group including five patients, lesions involved the efferent dentato-thalamo-cortical pathway and hypometria was associated with an imbalance between the rate of rise of the agonist EMG activity and the rate of rise of the antagonist EMG activity. In the three patients of group II, lesions were located at the level of the middle cerebellar peduncle, disrupting the crossed ponto-cerebellar projections. In these patients, the intensity of the agonist EMG activity was reduced and the duration of the antagonist EMG activity was increased. In the third group including seven patients presenting either a diffuse cerebellar atrophy or a stroke involving a large parenchymatous area, the agonist-antagonist EMG pattern showed a prolongation of the duration of the antagonist burst. Our results show that discrete mechanisms of cerebellar hypometria are associated with different anatomical lesions.

Invariability of the privileged direction of the maximal EMG activity during speed-related activation for reaching in the vertical plane.

Spatial tuning of goal-directed movements is a critical phenomenon for the central nervous system. The use of reliable models is a necessary step for the understanding of the neural mechanisms governing reaching movements. We analysed phasic electromyographic (EMG) activities associated with upper limb reaching movements in the vertical plane (12 targets) in seven healthy subjects during three successive sessions. We tested the hypothesis that one of the fundamental parameters of the directional tuning of phasic EMG activities is the peak of EMG activity. To characterize the tuning of phasic EMG activities for the seven recorded muscles (brachioradialis, biceps, medial and long head of triceps, anterior and posterior deltoid, latissimus dorsi), we digitally compressed the EMG activities corresponding to slow reaches to the same targets into the time frame of the fast EMG traces. Estimates of gravity-related components were subtracted. Peak of EMG activities in the resulting phasic traces were identified for each muscle and each target. The maximal peak EMG amongst the 12 peaks of EMG activity in the sagittal plane was called M Peak EMG. We defined the directional dominance as the ratio of the M Peak EMG divided by the Peak EMG in the opposite direction. The M Peak EMG for each muscle was always found in the same privileged direction of the movement, except for the latissimus dorsi. The directional dominance remained unchanged across recording sessions for the brachioradialis, anterior deltoid and posterior deltoid. However, the directional dominance increased across sessions for the biceps, medial head of triceps, long head of triceps and latissimus dorsi. The invariability of the privileged direction of the M peak EMG was thus observed for six of the seven muscles investigated. Therefore, we suggest that the selection of the privileged direction of the M Peak EMG represents a robust parameter to study the neuromuscular control strategy underlying the specification of movement direction.

Directional tuning of speed-related activation for reaching in the vertical plane in cerebellar ataxia.

The role of the cerebellum in the spatial tuning of goal-directed multi-joint movements in human is unknown. We analyzed the directional tuning of phasic EMG activities associated with upper limb reaching movements (12 targets) in the vertical plane in healthy subjects and in patients exhibiting cerebellar ataxia. Tuning of phasic EMG activities was investigated in seven muscles (brachioradialis, biceps, medial and long head of triceps, anterior and posterior deltoid, latissimus dorsi). We digitally compressed the EMG activities corresponding to slow reaches to the same targets into the time frame of the fast EMG traces. Estimates of gravity-related components were subtracted. Peaks of EMG activities in the resulting phasic traces were identified for each muscle and each target. Aberrant privileged directions of M Peak EMG (directions associated with the maximal peak of EMG amongst the 12 peaks of EMG activity in the sagittal plane) were found in all ataxic patients. Directional dominance, defined as the ratio of the M Peak EMG divided by the peak EMG in the opposite direction, was significantly higher in controls than in ataxic patients for one distal muscle (brachioradialis) and one proximal muscle (anterior deltoid). The spreading of EMG activities assessed by the global areas of the polar plots of phasic traces was broader in patients for the biceps and medial head of triceps. The distribution of densities of EMG activities (DDEMG) amongst the four quarters of the vertical plane, an index of the contrast in the intensities between quarters in polar plots, revealed increased values in control subjects for the brachioradialis, the biceps and the anterior deltoid as compared to ataxic patients. Representation of Net Vectors obtained from polar plots of peaks of EMG activities demonstrated an abnormal directional tuning in ataxic patients. In the majority of the cases, the Net Vector was outside the normal range for the following muscles: brachioradialis, biceps, anterior deltoid, posterior deltoid. This study reveals that cerebellar ataxia is associated with defective spatial properties of EMG activity during multiple joint movements. Privileged directions associated with M Peak EMG and Net Vectors are erroneous. We demonstrate that the cerebellum plays a determinant and unsuspected role in the spatial modulation of activation during speed-related action for reaching.

Shift from hypermetria to hypometria in multiple system atrophy: analysis of distal and proximal movements.

Dysmetria is a classical sign which designates the overshoot, also called hypermetria, and the undershoot, or hypometria, when the patient attempts to reach rapidly an aimed target. Dysmetria is typically observed in patients presenting a cerebellar dysfunction. Dysmetria of distal movements is associated with an imbalance between the timing and/or the intensity of agonist and antagonist EMG activities. So far, 1. there is only one description in human of a shift from hypermetria to hypometria for fast goal-directed single-joint movements during an aberrant recovery following a cerebellar infarction, and 2. such a shift has not been described for proximal movements. We report a patient presenting a multiple system atrophy (MSA). Initially, he exhibited a marked cerebellar syndrome. Fast wrist flexions and fast upper limb reaches in the sagittal plane were hypermetric. The distal hypermetria was associated with a delayed onset latency of the antagonist EMG activity and reduced intensities of both the agonist and the antagonist EMG activities. The proximal hypermetria was associated with a defect in the phasic spatial tuning of the EMG activities. He developed progressively severe extra-pyramidal signs. Distal hypermetria turned into hypometria, as a result of a decrease in the intensity of the agonist muscle. Proximal hypermetria turned into hypometria, as a result of the loss of directional preference of the EMG activities in proximal muscles. MSA is the second human model of a shift from hypermetria to hypometria.

Kinematics of fast wrist movements in manic-depressive illness chronically treated with lithium carbonate.

Lithium salts have been shown to impair kinematics of fast voluntary movements during acute intoxication. The aim of the present study was to determine whether lithium carbonate affected the kinematics of fast movements in patients chronically treated and who did not exhibit signs of neurotoxicity. We analysed fast wrist flexion movements in 6 healthy subjects, in 5 patients presenting a manic-depressive illness without treatment, and in 8 patients receiving lithium carbonate for a manic-depressive disease. The mean duration of treatment was 3.9 +/- 4.1 years, the mean daily dose 837 +/- 341 mg and the mean serum level 0.95 +/- 0.15 mEq/l. Although mean movement amplitudes were similar in the 3 groups, the variability of fast movements was increased in patients receiving lithium salts. The ratio of maximum to average velocities (Vm/Vave) was significantly higher in patients treated, and their movements were temporally asymmetrical, with a ratio of acceleration duration divided by deceleration duration being lower than in the 2 other groups. These kinematic abnormalities show that a chronic treatment with lithium salts is associated with an impairment of the cerebellar control of fast single-joint movements.

Isolated cerebellar dysarthria associated with a heat stroke.

Patients presenting with heat stroke may develop an acute pancerebellar syndrome. A patient presenting with an isolated cerebellar dysarthria after a heat stroke is reported. The dysarthria lasted two weeks. An isolated cerebellar dysarthria has been previously described in lesions of the paravermal zone of the rostral cerebellum. It is suggested that this region of the cerebellum is particularly vulnerable to fever.

Reversible cerebellar gait ataxia with postural tremor during episodes of high pyrexia.

We describe five patients presenting with high fever and isolated cerebellar gait ataxia. In all these patients, neurological examination revealed dysmetria, intention tremor and postural tremor during sustained posture, all restricted to the legs. Brain MRI was normal. In four of these patients, the recording of leg tremor during sustained postures showed a 3-Hz frequency. Cerebellar gait ataxia resolved within 3-10 days. We suggest that the ataxic gait was due to a reversible dysfunction of the spinocerebellar part of the anterior lobe.

Subacute pancerebellar syndrome associated with systemic lupus erythematosus.

A pancerebellar syndrome of subacute progression associated with cerebellar atrophy is highly suggestive of a paraneoplastic cerebellar degeneration (PCD). We describe a 27-year-old woman with systemic lupus erythematosus (SLE) that presented with a subacute pancerebellar syndrome. Serum and CSF anti-Yo, anti-Hu and anti-Ri antibodies were not found neither in blood, nor in CSF. Brain MRI showed a cerebellar atrophy. The cerebellar ataxia improved markedly following corticosteroids administration. This case probably demonstrates that an antineuronal antibody negative subacute cerebellar disease may not only be a manifestation of paraneoplastic disease, but that it can also be associated with SLE.

Cerebellar ataxia following whooping cough.

Bordetella pertussis (BP), the agent of whooping cough, has not been recognized so far as a cause of permanent cerebellar ataxia in human. We describe three patients who developed a disabling and permanent cerebellar syndrome soon after whooping cough. In two patients, diagnosis of BP infection was confirmed by culture of nasopharyngeal secretions. The infection occurred between the age of 13 and 15 years, with neurological symptoms beginning after a delay varying from 3 weeks to 3 months. In our three patients, the cerebellar syndrome was characterized by dysmetria of ocular saccades, scanning speech and ataxic gait. Brain MRI demonstrated a pancerebellar atrophy. The pathogenesis of this cerebellar degeneration is not established. Experimental studies have demonstrated that the cerebellum is particularly vulnerable to lymphocytosis-promoting factor (LPF), one of the exotoxins from BP. The mechanism of this toxicity might be a marked increase in the cellular levels of 3',5'cyclic guanosine monophosphate (cGMP). Since whooping cough is a bacterial exotoxin-mediated disease, this is the first report of a cerebellar syndrome triggered by a bacterial exotoxin.

[Interobserver reliability of a new horizontal pointing manoeuvre: comparison with conventional tests]. / Etude de la reproductibilité inter-observateur de l'évaluation d'une nouvelle manoeuvre de pointage horizontal: comparaison avec les tests cliniques conventionnels.

Finger-to-nose test, fine finger movements, to maintain arms against gravity, alternate movements of hands, Barany's test, muscle tone evaluation, Stewart-Holmes test and handwriting are the conventional clinical tests most frequently used in daily practice to evaluate voluntary movements of the upper limb. We describe a new clinical manoeuvre consisting of a horizontal pointing movement of one upper limb (the moving limb) towards the contralateral motionless limb. We have analyzed the reliability of our new test and of the conventional tests between 2 observers using kappa statistics in a group of 34 right-handed neurological patients. Agreement is very good for our test, since k has a value of 0.63 for left upper limb and a value of 0.64 for right upper limb. The only conventional test characterized by a higher interobserver reliability is handwriting. Furthermore, our manoeuvre is original, as attested by partial association coefficients analysis between our test and conventional tests. This might be due to the fact that our manoeuvre is the sole test investigating rapid proximal movements towards a fixed area in space. In conclusion, our horizontal pointing manoeuvre has a very good reliability between 2 observers and appears original.

[Lesions of ponto-cerebellar and olivo-cerebellar afferents demonstrated by neurophysiologic analysis]. / Atteinte des afférences ponto-cérébelleuses et olivo-cérébelleuses mise en évidence par l'analyse neurophysiologique.

We describe a 52-year-old woman presenting a 2-year history of limb clumsiness and gait difficulties, characterized by progressive worsening. Neurological examination revealed cerebellar intention tremor, cerebellar dysmetria of all 4 limbs and ataxic gait. However, brain MRI was normal. Analysis of fast wrist flexion movements demonstrated hypometric movements, with decreased intensities of agonist EMG activities and increased durations of antagonist EMG activities. Such EMG abnormalities have been demonstrated in patients presenting lesions of the middle cerebellar peduncle, affecting the crossed cerebellopontine projections. Moreover, adaptation motor learning during a pinch task (isometric force) showed a severe inability to adapt motor programming, indicating a disruption of cerebellolivary and cerebellopontine afferent systems. We suggest that our patient presented an exceptional brainstem syndrome involving the function of cerebellar inflow tracts. Such electrophysiological findings are not encountered in patients presenting a cerebellar cortical degeneration or cerebellovlivopontine atrophy, and might have important implications in the treatment of cerebellar ataxia in the future.

[Friedreich's ataxia: recent developments and prospects for treatment]. / L'ataxue de Fruedreucg: données récentes et perspectives thérapeutiques.

Friedreich's ataxia (FRDA) is the most frequent cause of recessive ataxias. Neurological examination shows oculo-motor ataxia, dysarthria, limbs ataxia, tendon areflexia, pyramidal signs and sensory deficits. Extra-neurological involvement consists in osteoarticular deformities, cardiomyopathy and diabetes mellitus. Neurological deficits and osteoarticular deformities both contribute to the gait disorder, which is the main disabling deficit. In 98% of the cases, a trinucleotide repeat is found in chromosome 9. Gene implicated in FRDA codes for a protein called frataxin. Experimental studies have revealed iron accumulation in mitochondria of neurons and cardiomyocytes, suggesting that frataxin plays a determinant role in intramitochondrial iron homeostasis. These discoveries are now considered as a clue for new strategies of treatment in this hereditary disease.

[Autosomal dominant spinocerebellar ataxia]. / Les ataxies spino-cérébelleuses (SCA) autosomiques dominantes.

The autosomal dominant spinocerebellar ataxias (SCA) are a heterogeneous group of degenerative diseases presenting with ataxic gait, limbs ataxia, dysarthria and cerebellar oculomotor disturbances. Usually, cerebellar signs are associated with pyramidal signs, extra-pyramidal signs, spinal signs and signs of peripheral neuropathy. Neuropathological studies have disclosed an involvement of the cerebellum and its afferent/efferent pathways, of the brainstem and of the spinal cord. Distinct entities are now recognized: SCA1, SCA2, SCA3/Machado-Joseph disease, SCA4, SCA5,SCA6, SCA7 and dentatorubropillidoluysian atrophy (DRPLA). In most cases, a CAG trinucleotide repeat expansion has been demonstrated by genetic investigations. Moreover, recent studies have shown that autosomal dominant spinocerebellar ataxias are characterized by intra-nuclear inclusions containing polyglutamine in affected cells. These complexes might pl ay a determinant role in the neurodegenerative process. Cell death could be due to accumulation of a polyglutamine as a result of trinucleotide repeats.