Idiopathic Paroxysmal Kinesigenic Dyskinesia Research Articles

Cerebello-thalamofrontal dysconnectivity in paroxysmal kinesigenic dyskinesia: A resting-state fMRI study

IntroductionThe pathophysiology of paroxysmal kinesigenic dyskinesia (PKD) remains elusive to date; however, several lines of evidence from neuroimaging studies suggest involvement of the basal ganglia-thalamocortical network in PKD. We combined fractional amplitude of low-frequency fluctuation (fALFF) and seed-based functional connectivity (FC) analyses in order to comprehensively investigate intrinsic brain activity alterations and their relationships with disease severity in patients with idiopathic PKD. MethodsResting-state functional MRI data were obtained and processed in 34 PKD patients and 34 matched controls. fALFF and seed-based FC maps were computed and compared between patients and controls. Linear regression analysis was further performed between regional fALFF values or FC strengths and clinical parameters in patients. ResultsPKD patients had a significant increase in fALFF in bilateral thalamus and cerebellum compared with controls. FC analysis seeding at the thalamic clusters revealed significant FC increases in motor cortex and supplementary motor area in PKD patients relative to controls. Longer disease duration was associated with increasing FC strength between the thalamus and motor cortex. ConclusionWe have provided evidence for abnormal intrinsic activity in the cerebello-thalamic circuit and increased thalamofrontal FC in PKD patients, implicating interictal cerebello-thalamofrontal dysconnectivity in the pathophysiology of PKD. Given the increasing FC strength in proportion to disease duration, the thalamofrontal hyperconnectivity might reflect either a consequence of recurrent dyskinesias on the brain or an innate pathology causing dyskinesias in PKD.

Levetiracetam Responsive in Late-Onset Idiopathic Paroxysmal Kinesigenic Dyskinesia

Levetiracetam Responsive in Late-Onset Idiopathic Paroxysmal Kinesigenic Dyskinesia

Thalamic involvement in paroxysmal kinesigenic dyskinesia: a combined structural and diffusion tensor MRI analysis.

Alteration of basal ganglia-thalamocortical circuit has been hypothesized to play a role in the pathophysiology underlying paroxysmal kinesigenic dyskinesia (PKD). We investigated macrostructural and microstructural changes in PKD patients using structural and diffusion tensor magnetic resonance imaging (MRI) analyses. Twenty-five patients with idiopathic PKD and 25 control subjects were prospectively studied on a 3T magnetic resonance (MR) scanner. Cortical thickness analysis was used to evaluate cortical gray matter (GM) changes, and automated volumetry and shape analysis were used to assess volume changes and shape deformation of the subcortical GM structures, respectively. Tract-based spatial statistics (TBSS) was used to evaluate white matter integrity changes in a whole-brain manner, and region-of-interest (ROI) analysis of diffusion tensor metrics was performed in subcortical GM structures. Compared to controls, PKD patients exhibited a reduction in volume of bilateral thalami and regional shape deformation mainly localized to the anterior and medial aspects of bilateral thalami. TBSS revealed an increase in fractional anisotropy (FA) of bilateral thalami and right anterior thalamic radiation in patients relative to controls. ROI analysis also showed an increase in FA of bilateral thalami in patients compared to controls. We have shown evidence for thalamic abnormalities of volume reduction, regional shape deformation, and increased FA in patients with PKD. Our novel findings of concomitant macrostructural and microstructural abnormalities in the thalamus lend further support to previous observations indicating causal relationship between a preferential lesion in the thalamus and development of PKD, thus providing neuroanatomical basis for the involvement of thalamus within the basal ganglia-thalamocortical pathway in PKD.

Exacerbation of idiopathic paroxysmal kinesigenic dyskinesia in remission state caused by secondary hypoparathyroidism with hypocalcemia after thyroidectomy: Evidence for ion channelopathy

Most reported cases of paroxysmal kinesigenic dyskinesia (PKD) are idiopathic or familial; however, hypoparathyroidism is another unusual cause of secondary PKD. The pathomechanism of PKD remains poorly understood, and the association between idiopathic and secondary PKD remains an enigma, and has yet to be clearly elucidated. We recently encountered a patient with idiopathic PKD whose symptoms were aggravated by secondary hypoparathyroidism with hypocalcemia after having undergone a thyroidectomy. The patient’s paroxysms were ameliorated by the normalization of serum calcium levels. The results discussed herein may provide support for the hypothesis that PKD is associated with neuronal ion regulation.

Alteration of Ictal and Interictal Perfusion in Patients with Paroxysmal Kinesigenic Dyskinesia

Although previous cerebral blood flow studies have suggested that the basal ganglia or thalamus are involved in the pathogenesis of paroxysmal kinesigenic dyskinesia (PKD), the precise anatomic substrate or pathophysiological networks associated with PKD remain unclear. Here, ictal and interictal single photon emission computed tomography (SPECT) in 2 patients with idiopathic PKD compared to 6 age-matched normal controls and the perfusion findings of subtraction ictal SPECT co-registered to MRI (SISCOM) in 1 patient are reported. The interictal and ictal perfusion changes were different in each of the patients and there were no consistent anatomic substrates observed. 2 patients had significant perfusion changes in the left frontal/temporal cortices compared to controls, whereas the others showed an increased uptake of 99mTc-ethyl cysteinate dimer (ECD) in the left occipital area on subtraction SPECT imaging. The results of this study suggest that the pathophysiology of PKD cannot be simply explained by lesions of the basal ganglia or thalamus, and that other associated areas of the cortex are likely involved in these movement disorders.

Idiopathic paroxysmal kinesigenic dyskinesia in Malaysia, a multi-racial Southeast Asian country

Paroxysmal kinesigenic dyskinesia is a rare disorder, and there are few reports of Asian patients with this condition. We reviewed the clinical features of all patients with idiopathic paroxysmal kinesigenic dyskinesia (PKD) seen at a major neurological centre in Malaysia. The charts of 11 patients with idiopathic PKD seen between 1995 and 2008 were reviewed retrospectively. The male:female ratio was 9:2. Ten patients were of Chinese ethnicity, and one was Malay. Three patients (from two families) had a family history of PKD. The involuntary movement was dystonia in 73% of patients. In one patient, attacks were precipitated by vestibular stimulation. One patient had generalized epilepsy. Another patient who did not have epilepsy demonstrated epileptiform discharges. Only slightly over one-quarter of patients had a positive family history. Males, and people of Chinese ancestry, seem to be affected more frequently by PKD in certain Asian populations.

Extended surround inhibition in idiopathic paroxysmal kinesigenic dyskinesia

Paroxysmal kinesigenic dyskinesia (PKD) is characterized by recurrent attacks of dyskinesia, in which movement of one body part produces involuntary movements of other body parts. Surround inhibition (SI), a mechanism for suppression of unwanted movements, could be deficient in these patients. To test this idea, we performed a transcranial magnetic stimulation (TMS) study in drug-naive patients with PKD. TMS was set to be triggered by self-initiated flexion of the index finger at different intervals. Average motor evoked potential (MEP) amplitudes obtained from self-triggered TMS were normalized to average MEPs of the control TMS at rest. Normalized MEP amplitudes of the patients' self-triggered TMS sessions at different intervals were compared to those of the controls. During index finger flexion, MEP amplitudes from the little finger muscle were unchanged in both the patients and normal subjects, however, post-movement MEP enhancement observed in the normal subjects was absent in patients with PKD. These results suggest that the functional operation of SI is itself preserved, but that post-movement excitation of surrounding muscles is deficient in PKD. This finding may represent that the operation of SI is extended to the post-movement period, perhaps as a compensatory mechanism for preventing unwanted movement in surrounding muscles. While many types of impaired inhibition have been described previously in PKD, this is the first possible example of increased inhibition.

Oxcarbazepine in Paroxysmal Dyskinesia

Four unrelated children (ages 8, 9, 16 and 17 years) with idiopathic paroxysmal kinesigenic dyskinesia responding to low dose oxcarbazepine are reported from the Department of Pediatric Neurology, Helen DeVos Children’s Hospital, Grand Rapids, MI.

Oxcarbazepine Use in Paroxysmal Kinesigenic Dyskinesia: Report on Four Patients

The paroxysmal dyskinesias are a heterogeneous group of movement disorders. They are distinguished from one another by the mechanism through which abnormal movements are induced. Paroxysmal kinesigenic dyskinesia is the most common subtype, consisting of involuntary dyskinesias induced by purposeful movements. It typically responds favorably to anticonvulsants. This retrospective review describes four unrelated children and adolescents with idiopathic paroxysmal kinesigenic dyskinesia who were treated with oxcarbazepine. Each patient achieved complete resolution of signs with low-dose oxcarbazepine monotherapy.

Clinical evaluation of idiopathic paroxysmal kinesigenic dyskinesia

Paroxysmal kinesigenic dyskinesia (PKD) is a rare disorder characterized by short episodes of involuntary movement attacks triggered by sudden voluntary movements. Although a genetic basis is suspected in idiopathic cases, the gene has not been discovered. Establishing strict diagnostic criteria will help genetic studies. The authors reviewed the clinical features of 121 affected individuals, who were referred for genetic study with a presumptive diagnosis of idiopathic PKD. The majority (79%) of affected subjects had a distinctive homogeneous phenotype. The authors propose the following diagnostic criteria for idiopathic PKD based on this phenotype: identified trigger for the attacks (sudden movements), short duration of attacks (<1 minute), lack of loss of consciousness or pain during attacks, antiepileptic drug responsiveness, exclusion of other organic diseases, and age at onset between 1 and 20 years if there is no family history (age at onset may be applied less stringently in those with family history). In comparing familial and sporadic cases, sporadic cases were more frequently male, and infantile convulsions were more common in the familial kindreds. Females had a higher remission rate than males. An infantile-onset group with a different set of characteristics was identified. A clear kinesigenic trigger was not elicited in all cases, antiepileptic response was not universal, and some infants had attacks while asleep. The diagnosis of idiopathic paroxysmal kinesigenic dyskinesia (PKD) can be made based on historical features. The correct diagnosis has implications for treatment and prognosis, and the diagnostic scheme may allow better focus in the search for the PKD gene(s).

Abnormal cortical and spinal inhibition in paroxysmal kinesigenic dyskinesia

Paroxysmal kinesigenic dyskinesia (PKD) is characterized by brief episodes of choreic/dystonic movements precipitated by sudden movement. The condition responds to antiepileptic medication, particularly carbemazepine. Autosomal dominant inheritance is often seen, and a locus in the pericentromeric region of chromosome 16 has been identified in some families. Little is known of the pathophysiology of PKD, although an ion channel abnormality is thought likely. We assessed a number of electrophysiological parameters in 11 patients with idiopathic PKD, a proportion of them on and off treatment. We identified reduced short intracortical inhibition (SICI), reduced early phase of transcallosal inhibition, and a reduced first phase of spinal reciprocal inhibition (RI) in subjects with PKD. The cortical silent period, the startle response and the second and third phases of RI were normal. Treatment with carbamazepine normalized the abnormalities in transcallosal inhibition, but had no effect on other parameters. Patients with PKD show a discrete set of abnormalities in cortical and spinal inhibitory circuits that differ from those seen in primary dystonia and epilepsy, and which may provide clues to the underlying pathophysiology of the disorder.

Clinical Features of Idiopathic Paroxysmal Kinesigenic Dyskinesia

The clinical features of 121 patients, referred for genetic study, with a presumptive diagnosis of idiopathic paroxysmal kinesigenic dyskinesia (PKD), were reviewed by a multicenter panel and reported from the University of Calfornia, San Francisco.

Proton MR spectroscopic findings in paroxysmal kinesigenic dyskinesia.

Although paroxysmal kinesigenic dyskinesia (PKD) has characteristic clinical features, the pathophysiology of PKD has remained unknown. The purpose of this study was to investigate the pathophysiology of idiopathic PKD by performing proton magnetic resonance spectroscopy (1H-MRS) in five patients with idiopathic PKD. Three patients were familial and two sporadic. Single-voxel 1H-MRS was performed on a GE 1.5-T SIGNA MR system. Localized 1H-MR spectra were obtained from the basal ganglia (n = 5), thalamus (n = 3), and supplementary motor area (SMA; n = 4) using STEAM sequence (stimulated echo acquisition mode; TR = 3.0 sec, TE = 30 msec, 64 AVG, volume = 8 mL) or PRESS (point resolved spectroscopy; TR = 3.0 sec, TE = 135 msec, volume = 4 mL). Peak ratios of Cho/Cr (Cho: choline, Cr: creatine) and mI/Cr (mI: myoinositol) were decreased significantly in the unilateral basal ganglia of two patients. In one, decreased peak ratio of mI/Cr in the unilateral basal ganglia was the only abnormality. In the remaining two, there was no significant abnormality. 1H-MR spectra obtained from the thalamus and SMA were all within normal limits. In conclusion, these results suggest that underlying pathophysiological mechanism of PKD may be at least partially associated with the dysfunction of cholinergic system in the basal ganglia.