Cerebellar Dysfunction In Patients Research Articles

A mini-review of the pathophysiology of task-specific tremor: insights from electrophysiological and neuroimaging findings

Task-specific tremor (TST) is a specific type of tremor that occurs when performing or attempting to perform a specific task, such as writing or playing a musical instrument. The clinical entity of TST remains heterogeneous. Some TSTs can only be induced by conducting a specific task, while others can be elicited when adopting a particular position simulating a task. The pathophysiology of TST is controversial. Whether TST is an isolated tremor syndrome, a spectrum of dystonic tremor syndrome (DTS), or essential tremor (ET) is not yet clear. Evidence from electrophysiological studies suggests that TST patients have normal reciprocal inhibition responses but abnormal motor cortical excitability, especially relating to the maladaptive long-interval intracortical inhibitory circuitry. The blink recovery study and eyeblink classical conditioning studies demonstrated possible hyperexcitability of the brainstem circuits and cerebellar dysfunction in patients with TST. Functional MRI studies have further shown that patients with TST have reduced functional connectivity in the cerebellum, similar to patients with DTS and ET. Due to variable methodologies and the sparsity of functional MRI studies in TST, it remains uncertain if patients with TST share the connectivity abnormalities between the cortical or subcortical areas that have been demonstrated in patients with DTS. Comprehensive electrophysiological and functional neuroimaging studies may help to elucidate the pathophysiology of TST.

New insights into cerebellar dysfunction in patients with delusional disorder: A systematic review

IntroductionThe cerebellum has been implicated in cognitive, affective and motor functions, including emotion regulation, executive control and sensorimotor processing. In schizophrenia, cerebellar dysfunction has been associated with treatment resistance and clinical features. However, few studies have been focused on delusional disorder (DD).ObjectivesOur main purpose was to review the evidence available on cerebellum abnormalities and dysfunctions in patients with DD.MethodsA systematic review was conducted through PubMed, Scopus and ClinicalTrials.gov (inception-June 2022) according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) directives. The following search terms were used: cerebellum OR cerebellar AND (“delusional disorder” AND paranoia). Reference lists from included studies were hand-checked to find other potential relevant papers.ResultsSix studies were included from a total of 119 retrieved records (PubMed: 52, Scopus: 66, ClinicalTrials.gov: 1). Study 1:Patients with DD somatic type (n=14) presented a decreased gray matter volume in cerebellar lobules compared to healthy controls (HC) (n=32, left lobule VIIIa) and non-somatic DD (n=18, lobule V). Cerebellar volumes did not seem to differ between HC and non-somatic DD. Study 2:Abnormalities of voluntary saccadic eye movements, linking frontal and cerebellar functions, were found in DD patients (n=34) compared to HC (n=40). Study 3: Abnormal smooth pursuit eye movements in DD (n=15) compared with HC (n=40) and similar to schizophrenia (n=40). Case reports (n=3): DD associated with Dandy-Walker variant (partial vermian hypoplasia), unruptured intracerebral aneurysm of basilar artery, and megacisterna magna.ConclusionsCerebellar deficits in patients with DD has been reported, particularly in those presenting somatic delusional contents.Disclosure of InterestNone Declared

3 Hz postural tremor: A specific and sensitive sign of cerebellar dysfunction in patients with cerebellar ataxia

Objective3 Hz postural tremor was described in patients with anterior cerebellar lobe atrophy, however sensitivity and specificity of this sign in degenerative cerebellar diseases has not yet been evaluated. Our aim was to assess the 3 Hz tremor in patients with cerebellar ataxia, compare its sensitivity and specificity with other posturography parameters and to find out a correlation of intensity of 3 Hz tremor with ataxia severity. Methods30 patients with degenerative cerebellar ataxia, a control group of 30 patients with compensated peripheral vestibulopathy and 40 healthy volunteers were examined by posturography. 3 Hz tremor was assessed both qualitatively and quantitatively, its sensitivity and specificity were compared with other standard posturography parameters. Results3 Hz postural tremor was detected in 90% of patients with cerebellar ataxia, with 100% specificity and 90% sensitivity. The sensitivity and specificity of quantitative analysis of 3 Hz tremor was largely superior to standard posturography parameters when differentiating patients with cerebellar ataxia from vestibular impairment and healthy controls. Conclusion3 Hz postural tremor is highly sensitive and specific sign of cerebellar impairment in patients with cerebellar ataxia. SignificanceEvaluation of 3 Hz postural tremor should be a standard part of posturography examination when considering a cerebellar impairment.

Rotational and Collic Vestibular-Evoked Myogenic Potential Testing in Normal Developing Children and Children With Combined Attention Deficit/Hyperactivity Disorder.

Vestibular dysfunction in childhood can have a major effect on a child's developmental process. Balance function has been reported to be poorer in children with attention deficit and hyperactivity disorder (ADHD) than in their typically developing peers. Due to contradictory available evidence and the paucity of research on vestibular function specifically in children with combined ADHD (cADHD), we designed this aged-matched study to assess vestibular function in children with cADHD. We enrolled 30 typically developing children (15 boys and 15 girls; mean age, 9 years 6 months; range, 7 to 12 years) and 33 children (19 boys and 14 girls; mean age, 9 years 0 months; range, 7 to 12 years) with cADHD diagnosed by our research psychiatrist. Typically developing controls were used to obtain normative data on vestibular testing and to examine the impact of age on the vestibular response parameters, and these results were compared with those of the cADHD group. All children underwent the sinusoidal harmonic acceleration subtype of the rotary chair test (0.01, 0.02, 0.08, 0.16, and 0.32 Hz) and the cervical vestibular-evoked myogenic potential (cVEMP) test. At all five frequencies in the sinusoidal harmonic acceleration test, there was no significant correlation between age and any of the following rotary chair response parameters in typically developing children: vestibulo-ocular reflex (VOR) gain, phase, asymmetry, and fixation index. Furthermore, there was no significant correlation between age and any of the following cVEMP parameters for the right and left ears of control group: p1 and n1 latency, amplitude, threshold, and amplitude ratio. Significantly higher VOR gains were observed for children with cADHD at frequencies of 0.01 (p = 0.001), 0.08 (p < 0.001), 0.16 (p = 0.001), and 0.32 (p = 0.003) Hz, when compared with the control group. Furthermore, fixation abilities were significantly lower in the cADHD group than in the control group at 0.16 (p < 0.001) and 0.32 (p < 0.001) Hz. cVEMP parameters showed no significant differences between the two groups. Our results showed higher VOR gains and poorer fixation abilities in children with cADHD compared with typically developing children. Cerebellar dysfunction in patients with ADHD has been well documented in the literature, and our findings of cVEMP and rotary chair tests for these children showed impaired vestibular function in these children, based on increased VOR gain values and decreased fixation capabilities. Because VOR gain is mediated through the inferior olive and controlled by the cerebellum, our results suggest that central inhibition of vestibular function may be deficient in children with cADHD, resulting in higher VOR gains. Also, there is general agreement that failure of fixation suppression indicates a central lesion. The lesion can originate from the parietal-occipital cortex, the pons, or the cerebellum. However, failure of fixation suppression is most prominent in lesions involving the midline cerebellum that could be counted for children with cADHD. We believe that this contribution is theoretically and practically relevant as high VOR gains and decreased suppression capabilities may result in symptoms of reading and writing difficulties, learning disabilities, vertigo, and motion sickness in these children. Therefore, assessment of vestibular function in children with cADHD at a young age must be considered when developing rehabilitation protocols for these children.

Subclinical cerebellar dysfunction in patients with migraine: Evidence from eyeblink conditioning

Clinical findings suggest cerebellar dysfunction in patients with migraine. Eyeblink classical conditioning (EBCC) is a simple form of associative learning which depends on the integrity of the cerebellum. The aim of this study was to assess whether EBCC is disturbed in patients with migraine. A delay conditioning paradigm was used in the headache-free interval in 32 female patients with migraine, in 24 of them without (MwoA) and eight with aura (MwA), and in 32 age-matched female controls. As primary outcome measure acquisition and as secondary outcome measures timing and extinction of conditioned eyeblink responses (CR) were assessed. CR acquisition was significantly reduced in all migraine patients (mean total CR incidence 35.2 ± 22.1%) compared to controls (54.7 ± 21.3%; p < 0.001; Bonferroni-corrected p level < 0.025) and in MwA patients (19.9 ± 20.2%) compared to matched controls (58.2 ± 27.0%; p = 0.006) but not in MwoA patients (40.3 ± 20.6%) compared to matched controls (53.6 ± 19.7%; p = 0.028; Bonferroni-corrected p level < 0.0166). Decrease of CR incidences in MwA patients was not significantly different compared to MwoA patients (p = 0.021; Bonferroni-corrected p level < 0.0166). CR timing and extinction was not affected in migraine patients. Reduced acquisition of CRs in the cohort of female patients studied here supports findings of a cerebellar dysfunction in migraine.

Impaired saccadic adaptation in schizophrenic patients with high neurological soft sign scores

Many motor and cognitive alterations in schizophrenia suggest the involvement of the cerebellum. Neurological soft signs (NSS) are frequent in patients with schizophrenia and reductions in cerebellar volume have been associated with high NSS scores. In this study, we tested saccadic adaptation, a well-characterised oculomotor paradigm involving the cerebellum, in schizophrenic patients with high NSS scores. We used a backward reactive saccade adaptation task, in which the target moves intrasaccadically toward initial fixation, causing the saccade to complete with an endpoint error. A group of 12 schizophrenic patients (SZ; DSM IV) with high NSS scores was compared to a group of 13 matched healthy controls (HC). SZ patients showed lower saccade adaptation than HC. Nevertheless, the time course of adaptation was similar for both groups. This study indicates cerebellar dysfunction in patients with schizophrenia and high NSS scores. Part of the deficit seen in schizophrenia may have a cerebellar origin.

Multiple sclerosis tremor and the Stewart-Holmes manoeuvre.

The objective of this study is to define tremor and cerebellar dysfunction and determine whether kinetic and postural tremor correlate with cerebellar dysfunction in patients with multiple sclerosis (MS). Cerebellar symptoms such as dysmetria often interfere with tremor evaluation in MS. The Stewart-Holmes (SH) manoeuvre, which has been recently quantified, may offer a selective evaluation of cerebellar dysfunction in such patients. Thirty-two patients with definite MS and arm tremor were evaluated (simplified Fahn tremor scale for kinetic and postural tremor, finger-to-nose test, clinical SH manoeuvre, quantitative study of the SH manoeuvre). Median severity of kinetic and postural tremor on the most disabled side was, respectively, 2 (range 0-4) and 1.5 (range 0-4). Clinical SH scores were moderately correlated to quantified SH measures (r = 0.36, P < 0.05). Kinetic and postural tremors were strongly correlated (r = 0.73, P < 0.0001) but did not correlate with clinical or quantified SH scores. Patients with bilateral tremor had higher scores for quantified SH, and a trend to higher clinical SH and finger-to-nose scores than patients with unilateral tremor. Although clinically associated, cerebellar dysfunction and tremor may be partly independent symptoms, suggesting they may relate to dysfunction of different neuronal systems. The SH manoeuvre should be part of the evaluation of MS patients considered for surgery of tremor.

Magnetic stimulation over the cerebellum in patients with ataxia

We studied 20 patients with ataxia caused by various disorders using magnetic stimulation over the cerebellum. Results were compared with normal values found for 12 normal volunteers. In normal subjects, a magnetic stimulus over the cerebellum reduced the size of responses evoked by magnetic cortical stimulation when it preceded cortical stimulus by 5, 6 and 7 ms. The grand average of the ratios of the areas of conditioned responses at intervals of 5, 6 and 7 ms to those of control responses was designated the average area ratio (5–7 ms). Suppression of motor cortical excitability was reduced or absent in patients with a lesion in the cerebellum or cerebellothalamocortical pathway, but was normal in patients with a lesion in the afferent pathway to the cerebellum. Normal suppression was observed in Fisher's syndrome. The average area ratio (5–7 ms) correlated well with the severity of ataxia in patients with degenerative late-onset ataxia. These results are consistent with those for electrical stimulation of the cerebellum reported previously. We conclude that magnetic stimulation over the cerebellum produces the same effect as electrical stimulation even in ataxic patients. This less painful method can be used clinically to clarify the pathomechanisms for ataxia. Two other clinical uses of this technique were that it revealed clinically undetectable cerebellar dysfunction in patients whose extrapyramidal signs masked cerebellar signs, and that the slow progression of ataxia could be followed quantitatively in patients with degenerative late-onset ataxia.

Cerebellar dysfunction in patients with bronchogenic carcinoma: clinical and posturographic findings.

Neurological examination and posturography showed cerebellar signs in 13 of 50 unselected patients with bronchogenic carcinoma not complicated by other diseases. The occurrence of cerebellar signs did not depend on the histological type of tumour or the extent of tumour spread. Most of the clinically affected patients had mild to pronounced cerebellar atrophy, revealed by CT. The correlation between the amount of CT-confirmed atrophy and the severity of clinical symptoms, however, was poor. Since other reasons for cerebellar dysfunction (e.g. chemotherapy, chronic alcoholism, metastases) were excluded, cerebellar signs were attributed to paraneoplastic cerebellar degeneration or to a consequence of severe neoplastic illness. The high incidence of cerebellar dysfunction in patients with bronchogenic carcinoma confirms the frequent histopathological finding of cortical cerebellar degeneration in malignant disease.

Cerebellar dysfunction in patients with bronchogenic carcinoma: immunological investigations.

Sera from seven patients with bronchogenic carcinoma and cerebellar dysfunction were tested for anti-Purkinje cell antibodies (APCA) by indirect immunofluorescence and indirect immunoperoxidase reaction. Specific APCA as described in paraneoplastic cerebellar degeneration (PCD) were not detected in any of these patients or in control patients. The lack of APCA in patients with bronchogenic carcinoma and their presence in association with ovarian or breast cancer indicate that different pathogenetic mechanisms may play a role in PCD.