Consensus Paper: Ataxic Gait.

The aim of this consensus paper is to discuss the roles of the cerebellum in human gait, as well as its assessment and therapy. Cerebellar vermis is critical for postural control. The cerebellum ensures the mapping of sensory information into temporally relevant motor commands. Mental imagery of gait involves intrinsically connected fronto-parietal networks comprising the cerebellum. Muscular activities in cerebellar patients show impaired timing of discharges, affecting the patterning of the synergies subserving locomotion. Ataxia of stance/gait is amongst the first cerebellar deficits in cerebellar disorders such as degenerative ataxias and is a disabling symptom with a high risk of falls. Prolonged discharges and increased muscle coactivation may be related to compensatory mechanisms and enhanced body sway, respectively. Essential tremor is frequently associated with mild gait ataxia. There is growing evidence for an important role of the cerebellar cortex in the pathogenesis of essential tremor. In multiple sclerosis, balance and gait are affected due to cerebellar and spinal cord involvement, as a result of disseminated demyelination and neurodegeneration impairing proprioception. In orthostatic tremor, patients often show mild-to-moderate limb and gait ataxia. The tremor generator is likely located in the posterior fossa. Tandem gait is impaired in the early stages of cerebellar disorders and may be particularly useful in the evaluation of pre-ataxic stages of progressive ataxias. Impaired inter-joint coordination and enhanced variability of gait temporal and kinetic parameters can be grasped by wearable devices such as accelerometers. Kinect is a promising low cost technology to obtain reliable measurements and remote assessments of gait. Deep learning methods are being developed in order to help clinicians in the diagnosis and decision-making process. Locomotor adaptation is impaired in cerebellar patients. Coordinative training aims to improve the coordinative strategy and foot placements across strides, cerebellar patients benefiting from intense rehabilitation therapies. Robotic training is a promising approach to complement conventional rehabilitation and neuromodulation of the cerebellum. Wearable dynamic orthoses represent a potential aid to assist gait. The panel of experts agree that the understanding of the cerebellar contribution to gait control will lead to a better management of cerebellar ataxias in general and will likely contribute to use gait parameters as robust biomarkers of future clinical trials.

The Yin and Yang of Operating on a Posterior Fossa Meningioma: The Schmahmann Syndrome.

The cerebellum is classically linked with control of motor function, such as coordination, balance, and regulation of movement. There is an increasing awareness, now, of the non-motor functions of the cerebellum, and the occurrence of behavioral anomalies with cerebellar disorders. We present the first report of Schmahmann syndrome (cerebellar cognitive affective syndrome [CCAS]) occurring secondary to posterior fossa meningioma excision. A 35-year-old lady with a posterior fossa meningioma developed an infarct of the right posterosuperior cerebellar hemisphere and ipsilateral superior vermis, following suboccipital craniotomy and tumor resection. Few days after the surgery, she presented with aggressive and emotional behavior, irrelevant talk, and emotional lability. The CCAS scale was administered, and she scored poorly on almost all parameters. A neuropsychological evaluation was also done. The occurrence of CCAS, posterior fossa syndrome (PFS), and behavioral abnormalities like abnormal pathological laughter/crying provides further clinical evidence of the "affective" functions of the cerebellum, modulated mainly by the posterior lobe and vermis of the cerebellum.

Cerebral folate deficiency in adults: A heterogeneous potentially treatable condition.

OBJECTIVE: To describe the phenotype and the response to folinic acid supplementation of cerebral folate deficiency (CFD) in adults, a disorder diagnosed on low 5-methyltetrahydro-folate (5MTHF) in cerebrospinal fluid (CSF), which can correspond to a inherited disorder of folate metabolism (IDFM) or to a metabolic consequence of various neurological diseases. METHODS: We conducted a retrospective study on 224 adult patients with neurological symptoms who had a 5MTHF CSF dosage, collecting their neurologic and neuroimaging data. RESULTS: 69 patients had CFD (CSF 5MTHF level < 41 nmol/L), 25 of them had severe CFD (sCFD; ≤25 nmol/L) with adult onset neurological symptoms in 41%. 56% of sCFD patients had an underlying identified neurologic disorder, mainly mitochondrial diseases, hepatic encephalopathy and primary brain calcifications (no identified IDFM), the others were classified as undiagnosed. sCFD patients presented most frequently pyramidal syndrome (75%), movement disorders (56%), cerebellar syndrome (50%) and intellectual disability (46%). MRI findings mostly showed white matter abnormalities (WMA; 32%) and calcifications (12%), and were normal in 23%. The clinico-radiological phenotype of sCFD patients was not clearly different from non CFD patients in terms of manifestations frequency. However, their neurological picture was more complex with a higher number of combined neurological symptoms (4.7±1.6 vs 3.4±1.7, p = .01). In Magnetic Resonance Spectroscopy (MRS), Choline/Creatine (Cho/Cr) ratio was lower in sCFD patients (n = 7) compared to non-CFD patients (n = 73) (p = .005), with good sensitivity (71%) and excellent specificity (92%). Among twenty-one CFD patients treated with folinic acid, nine had a sustained improvement, all with sCFD but one (50% of sCFD patients improved). In two undiagnosed patients with extremely low 5MTHF CSF values, MRI WMA and low Cho/Cr ratios, folinic acid treatment leaded to a dramatic clinical and radiological improvement. CONCLUSION: CSF 5MTHF dosage should be considered in patients with mitochondrial diseases, primary brain calcifications and unexplained complex neurological disorders especially if associated with WMA, since folinic acid supplementation in patients with sCFD is frequently efficient.

Insights from ERPs into attention during recovery after cerebellar stroke: a case report.

The role of the cerebellum in cognitive performance and attentional processes is a focus of research in recent years. We investigated the P300 component in a patient with a left posterior cerebellar ischemic stroke during both the acute phase and over 4 weeks of follow-up. After stroke, auditory event-related potentials showed a reduction in P3 amplitude, which appears to improve instead after 4 weeks of follow-up. These event-related potential findings could suggest a specific neural pattern of disruption in selective attention during the discrimination processes of the stimulus following a posterior cerebellar lesion. A recovery is observed in the long term.

Your actions in my cerebellum: subclinical deficits in action observation in patients with unilateral chronic cerebellar stroke.

Empirical evidence indicates that cognitive consequences of cerebellar lesions tend to be mild and less important than the symptoms due to lesions to cerebral areas. By contrast, imaging studies consistently report strong cerebellar activity during tasks of action observation and action understanding. This has been interpreted as part of the automatic motor simulation process that takes place in the context of action observation. The function of the cerebellum as a sequencer during executed movements makes it a good candidate, within the framework of embodied cognition, for a pivotal role in understanding the timing of action sequences. Here, we investigated a cohort of eight patients with chronic, first-ever, isolated, ischemic lesions of the cerebellum. The experimental task consisted in identifying a plausible sequence of pictures from a randomly ordered group of still frames extracted from (a) a complex action performed by a human actor ("biological action" test) or (b) a complex physical event occurring to an inanimate object ("folk physics" test). A group of 16 healthy participants was used as control. The main result showed that cerebellar patients performed significantly worse than controls in both sequencing tasks, but performed much worse in the "biological action" test than in the "folk physics" test. The dissociation described here suggests that observed sequences of simple motor acts seem to be represented differentially from other sequences in the cerebellum.

Pitch discrimination in cerebellar patients: evidence for a sensory deficit.

In the last two decades, a growing body of research showing cerebellar involvement in an increasing number of nonmotor tasks and systems has prompted an expansion of speculations concerning the function of the cerebellum. Here, we tested the predictions of a hypothesis positing cerebellar involvement in sensory data acquisition. Specifically, we examined the effect of global cerebellar degeneration on primary auditory sensory function by means of a pitch discrimination task. The just noticeable difference in pitch between two tones was measured in 15 healthy controls and in 15 high functioning patients afflicted with varying degrees of global cerebellar degeneration caused by hereditary, idiopathic, paraneoplastic, or postinfectious pancerebellitis. Participants also performed an auditory detection task assessing sustained attention, a test of verbal auditory working memory, and an audiometric test. Patient pitch discrimination thresholds were on average five and a half times those of controls and were proportional to the degree of cerebellar ataxia assessed independently. Patients and controls showed normal hearing thresholds and similar performance in control tasks in sustained attention and verbal auditory working memory. These results suggest there is an effect of cerebellar degeneration on primary auditory function. The findings are consistent with other recent demonstrations of cerebellar-related sensory impairments, and with robust cerebellar auditorily evoked activity, confirmed by quantitative meta-analysis, across a range of functional neuroimaging studies dissociated from attention, motor, affective, and cognitive variables. The data are interpreted in the context of a sensory hypothesis of cerebellar function.

Eye-blink conditioning deficits indicate temporal processing abnormalities in schizophrenia.

Theoretical models suggest that symptoms of schizophrenia may be due to a dysfunctional modulatory system associated with the cerebellum. Although it has long been known that the cerebellum plays a critical role in associative learning and motor timing, recent evidence suggests that it also plays a role in nonmotor psychological processes. Indeed, cerebellar anomalies in schizophrenia have been linked to cognitive dysfunction and poor long-term outcome. To test the hypothesis that schizophrenia is associated with cerebellar dysfunction, cerebellar-dependent, delay eye-blink conditioning was examined in 62 individuals with schizophrenia and 62 age-matched non-psychiatric comparison subjects. The conditioned stimulus was a 400 ms tone, which co-terminated with a 50 ms unconditioned stimulus air puff. A subset of participants (25 with schizophrenia and 29 controls) also completed the Wechsler Abbreviated Scale of Intelligence. Participants with schizophrenia exhibited lower rates of eye-blink conditioning, including earlier (less adaptively timed) conditioned response latencies. Cognitive functioning was correlated with the rate of conditioned responsing in the non-psychiatric comparison subjects but not among those with schizophrenia, and the magnitude of these correlations significantly differed between groups. These findings are consistent with models of schizophrenia in which disruptions within the cortico-cerebellar-thalamic-cortical (CCTC) brain circuit are postulated to underlie the cognitive fragmentation that characterizes the disorder.

The phenomenon of spasticity: a pathophysiological and clinical introduction to neuromodulation therapies.

Spasticity is part of the complex clinical picture which results from the upper motor neuron impairment. The underlying mechanisms that produce the automatic overactivity of the muscle groups may manifest themselves as either passive movements dependent on the exerted velocity or persistent muscle overactivity in the form of spastic dystonia. The therapeutic management of spasticity is closely related to the aims of rehabilitation; these include avoidance of complications, restoration of movement, re-education of motion and gait, development of self-dependency, and social integration, as well as modification and reorganization of the cortical brain map. The latter is achieved through long-term learning processes which are subserved by new neurophysiological dynamics. and the mechanisms of neuroplasticity which develop during neural regeneration.

The effect of deep brain stimulation on quality of life in movement disorders.

Deep brain stimulation (DBS) is a viable treatment alternative for patients with Parkinson's disease (PD), essential tremor (ET), dystonia, and cerebellar outflow tremors. When poorly controlled, these disorders have detrimental effects on the patient's health related quality of life (HRQoL). Instruments that measure HRQoL are useful tools to assess burden of disease and the impact of therapeutic interventions on activities of daily living, employment, and other functions. We systematically and critically reviewed the literature on the effects of DBS on HRQoL in PD, ET, dystonia, and cerebellar outflow tremor related to multiple sclerosis.

Tremor cells in the human thalamus: differences among neurological disorders.

OBJECT: Thalamic neurons firing at frequencies synchronous with tremor are thought to play a critical role in the generation and maintenance of tremor. The authors studied the incidence and locations of neurons with tremor-related activity (TRA) in the thalamus of patients with varied pathological conditions-including Parkinson disease (PD), essential tremor (ET), multiple sclerosis (MS), and cerebellar disorders--to determine whether known differences in the effectiveness of thalamic stereotactic procedures for these tremors could be correlated to differences in the incidence or locations of TRA cells. METHODS: Seventy-five operations were performed in 61 patients during which 686 TRA cells were recorded from 440 microelectrode trajectories in the thalamus. The locations of the TRA cells in relation to electrophysiologically defined thalamic nuclei and the commissural coordinates were compared among patient groups. The authors found that TRA cells are present in patients with each of these disorders and that these cells populate several nuclei in the ventral lateral tier of the thalamus. There were no large differences in the locations of TRA cells among the different diagnostic classes, although there was a difference in the incidence of TRA cells in patients with PD, who had greater than 3.8 times more cells per thalamic trajectory than patients with ET and approximately five times more cells than patients with MS or cerebellar disorders. CONCLUSIONS: There was an increased incidence of TRA in the thalamus of patients with PD. The location of thalamic TRA cells in patients with basal ganglia and other tremor disorders was similar.

Single-neuron analysis of human thalamus in patients with intention tremor and other clinical signs of cerebellar disease.

Tremor that occurs as a result of a cerebellar lesion, cerebellar tremor, is characteristically an intention tremor. Thalamic activity may be related to cerebellar tremor because transmission of some cerebellar efferent signals occurs via the thalamus and cortex to the periphery. We have now studied thalamic neuronal activity in a cerebellar relay nucleus (ventral intermediate-Vim) and a pallidal relay nucleus (ventralis oral posterior-Vop) during thalamotomy in patients with intention tremor and other clinical signs of cerebellar disease (tremor patients). The activity of single neurons and the simultaneous electromyographic (EMG) activity of the contralateral upper extremity in tremor patients performing a pointing task were analyzed by spectral cross-correlation analysis. EMG spectra during intention tremor often showed peaks of activity in the tremor-frequency range (1.9-5.8 Hz). There were significant differences in thalamic neuronal activity between tremor patients and controls. Neurons in Vim and Vop had significantly lower firing rates in tremor patients than in patients undergoing thalamic surgery for pain (pain controls). Other studies have shown that inputs to Vim from the cerebellum are transmitted through excitatory connections. Therefore the present results suggest that tremor in these tremor patients is associated with deafferentation of the thalamus from cerebellar efferent pathways. The thalamic X EMG cross-correlation functions were studied for cells located in Vim and Vop. Neuronal and EMG activity were as likely to be significantly correlated for cells in Vim as for those in Vop. Cells in Vim were more likely to have a phase lag relative to EMG than were cells in Vop. In monkeys, cells in the cerebellar relay nucleus of the thalamus, corresponding to Vim, are reported to lead movement during active oscillations at the wrist. In view of these monkey studies, the present results suggest that cells in Vim are deafferented and have a phase lag relative to tremor that is not found in normal active oscillations. The difference in phase of thalamic spike X EMG activity between Vim and Vop may contribute to tremor because lesions of pallidum or Vop are reported to relieve cerebellar tremor.

Attenuation of pathological tremors by functional electrical stimulation. II: Clinical evaluation.

In this study we evaluated a technique for tremor suppression with functional electrical stimulation (FES), the technical details of which were described in the previous paper. Three groups of patients were investigated: those with essential tremor, parkinsonian tremor, and cerebellar tremor associated with multiple sclerosis. In each group, tremor was attenuated by significant amounts (essential tremor: 73%; parkinsonian tremor: 62%; cerebellar tremor: 38%). These attenuations were in good accord with predictions based on the dynamic analyses and filter designs derived in the previous paper. With filters "tuned" to the lower mean tremor frequency encountered in the cerebellar patients, more attenuation was possible in this group as well. We identified some practical limitations in the clinical application of the technique in its present form. The most important was that in daily use, only one antagonist pair of muscles can realistically be controlled. At first sight, this restricts the usefulness of the system to patients with single-joint tremors. However, the concomitant use of mechanical orthoses may broaden the scope of application.

[Impairment of the accuracy of tracking movements in lesions of the cerebellum and pyramidal system in man]. / Narusheniia tochnostnykh slediashchikh dvizhenii pri porazhenii mozzhechka i piramidnoi sistemy u cheloveka.

Kinematic and electromyographic characteristics of step-tracking movements performed with and without visual guidance have been studied in 3 groups of patients suffering from hereditary lesions of intermedial and lateral systems of the cerebellum and pyramidal tract. Lesions of the intermedial cerebellum not changing parameters of the first preprogrammed component altered deeply the maintenance phase that was performed as large oscillations around a required level. Lesions of the lateral cerebellum, on the contrary, were followed by inability to control accurately the amplitude of steps which were performed with a constant hypermetric error; the maintenance phase of movement was not disturbed in this group. In patients suffering from pyramidal lesions the initial rapid limb position adjustment was replaced by slow approximating tracking; the maintenance component of the movement was performed with fluctuations and constant drift towards the ground. It is concluded that whereas the lateral cerebellar system is involved in central motor program mechanisms, the intermedial cerebellum is essential for accurate postural maintenance.

[Central alveolar hypoventilation as a complication of massive intracerebellar hemorrhage: report of a case treated by diaphragm pacing].

The author reported a case of central alveolar hypoventilation (Ondine's curse) which was treated by diaphragm pacing. A 59-year-old man was admitted because of sudden deep coma and tetraparesis. Neurological examination on admission showed miotic pupils with absent light reaction, no oculocephalic reflex, no corneal reflex and tetraparesis. Glasgow scale was evaluated to be E-1 V-1, and M-3 with total of 5 points. Computed tomography confirmed a large hematoma in the cerebellum with ventricular rupture. Immediately, a suboccipital craniectomy was performed and the hematoma was evacuated. His neurological condition was improved gradually within a month after the operation. He responded to verbal orders and moved all his limbs against gravity. His respiration, however, was irregular with a pattern of so-called "cluster breathing" followed by prolonged apnea, that was more pronounced in night. He was suffered from hypoxic hypercapnea and recurrent pneumonia. Therefore, authors decided to employ diaphragm pacing for management of central alveolar hypoventilation. A diaphragm pacemaker (radiofrequency induction) was implanted. A cuff electrode was put around the right phrenic nerve in the right thorax, and the receiver installed subcutaneously in the right anterior chest. Postoperative respiratory study showed ventilation on pacing with satisfactory blood gas and he became able to move around using a wheel chair. In 1966 Glenn demonstrated a new technique to move the diaphragm paced by a receiver through the phrenic nerve, triggered by radio wave from external device.(ABSTRACT TRUNCATED AT 250 WORDS)

Blind loop syndrome, vitamin E malabsorption, and spinocerebellar degeneration.

A 72-year-old man had severe malabsorption, progressive retinopathy, and spinocerebellar degeneration 32 years after gastric surgery, blind loop formation, and intestinal bacterial overgrowth. Clinical and pathologic features were typical of vitamin E deficiency; vitamin E was nearly undetectable in serum and profoundly low in adipose tissue. Vitamin E blood levels initially improved on treatment with antibiotics; after additional vitamin E supplementation, there was clinical improvement.

[Diaphragm pacemaker implantation: a case report of central hypoventilation due to cerebellar bleeding].

A 60-year-old male developed chronic respiratory failure due to central hypoventilation after cerebellar bleeding. We implanted a diaphragm pacemaker (radio-frequency type) to the patient, and his respiratory status was improved. Although this apparatus devised by Glenn has been widely used in the United States, clinical applications in Japan were rarely reported. Diaphragm pacing might be one of the effective treatments to the patient with chronic respiratory failure. We discussed the indication, mechanical subject and surgical approach concerning diaphragm pacemaker implantation in this paper.

Cerebellar pathology in schizophrenia--cause or consequence?

Atrophy of the cerebellar vermal cortex has been reported to occur in 10% or more of patients with schizophrenia. Data from studies on experimental animals indicate that a functional relationship between the cerebellum and parts of the forebrain involved in emotion exists, and that the cerebellum may influence some types of behavior. Cerebellar abnormality in schizophrenic patients, although of uncertain cause, could contribute to the symptomatology of the disease.