Extracerebellar Signs and Symptoms in 117 Korean Patients with Early-Stage Spinocerebellar Ataxia

Background@#and Purpose Spinocerebellar ataxias (SCAs) are the most common form of hereditary ataxias. Extracerebellar signs have been well described and are helpful in differentiating the SCA subtypes. However, there are few reports on the early-stage extracerebellar signs in various SCA subtypes. This study explored the clinical and magnetic resonance imaging (MRI) characteristics of early-stage SCAs in the Korean population. @*Methods@#We retrospectively reviewed the medical records of genetically confirmed SCA patients with a disease duration of <5 years. Data on baseline characteristics, extracerebellar signs, and initial MRI findings were organized based on SCA subtypes. @*Results@#This study included 117 SCA patients with a median age at onset of 40.6 years. The family history was positive in 71.8% of the patients, and the median disease duration and the score on the Scale for the Assessment and Rating of Ataxia at the initial visit were 2.6 years and 5.0, respectively. SCA3 was the most prevalent subtype, and oculomotor abnormalities were the most frequent extracerebellar signs in early-stage SCAs. Saccadic slowing was characteristic of SCA2 and SCA7, and gaze-evoked nystagmus was prominent in SCA6. Parkinsonism was relatively frequent in SCA8 and SCA3. Decreased visual acuity was specific for SCA7. Dementia was not an early manifestation of SCAs. Brain MRI revealed a pattern of pontocerebellar atrophy in SCA2 and SCA7, while SCA6 demonstrated only cerebellar cortical atrophy. @*Conclusions@#SCA patients exhibited diverse extracerebellar signs even in the early stage.Specific extracerebellar signs were characteristic of specific subtypes, which could facilitate differential diagnoses of early-stage SCAs.

Extracerebellar Signs and Symptoms in 117 Korean Patients with Early-Stage Spinocerebellar Ataxia

Background@#and Purpose Spinocerebellar ataxias (SCAs) are the most common form of hereditary ataxias. Extracerebellar signs have been well described and are helpful in differentiating the SCA subtypes. However, there are few reports on the early-stage extracerebellar signs in various SCA subtypes. This study explored the clinical and magnetic resonance imaging (MRI) characteristics of early-stage SCAs in the Korean population. @*Methods@#We retrospectively reviewed the medical records of genetically confirmed SCA patients with a disease duration of <5 years. Data on baseline characteristics, extracerebellar signs, and initial MRI findings were organized based on SCA subtypes. @*Results@#This study included 117 SCA patients with a median age at onset of 40.6 years. The family history was positive in 71.8% of the patients, and the median disease duration and the score on the Scale for the Assessment and Rating of Ataxia at the initial visit were 2.6 years and 5.0, respectively. SCA3 was the most prevalent subtype, and oculomotor abnormalities were the most frequent extracerebellar signs in early-stage SCAs. Saccadic slowing was characteristic of SCA2 and SCA7, and gaze-evoked nystagmus was prominent in SCA6. Parkinsonism was relatively frequent in SCA8 and SCA3. Decreased visual acuity was specific for SCA7. Dementia was not an early manifestation of SCAs. Brain MRI revealed a pattern of pontocerebellar atrophy in SCA2 and SCA7, while SCA6 demonstrated only cerebellar cortical atrophy. @*Conclusions@#SCA patients exhibited diverse extracerebellar signs even in the early stage.Specific extracerebellar signs were characteristic of specific subtypes, which could facilitate differential diagnoses of early-stage SCAs.

Successful Pallidal Stimulation in a Patient with KMT2B-Related Dystonia

Although the KMT2B gene was identified as a causative gene for early-onset generalized dystonia, the efficacy of deep brain stimulation (DBS) in KMT2B-related dystonia has not been clearly elucidated. Here, we describe a 28-year-old woman who developed generalized dystonia with developmental delay, microcephaly, short stature, and cognitive decline. She was diagnosed with KMT2B- related dystonia using whole-exome sequencing with a heterozygous frameshift insertion of c.515dupC (p.T172fs) in the KMT2B gene. Oral medications and botulinum toxin injection were not effective. The dystonia markedly improved with bilateral pallidal DBS (the Burke-Fahn-Marsden Dystonia Rating Scale score was reduced from 30 to 5 on the dystonia movement scale and from 11 to 1 on the disability scale), and she could walk independently. From this case, we suggest that bilateral globus pallidus internus DBS can be an effective treatment option for patients with KMT2B-related generalized dystonia.

The Effect of Globus Pallidus Interna Deep Brain Stimulation on a Dystonia Patient with the GNAL Mutation Compared to Patients with DYT1 and DYT6

OBJECTIVE: The aim of this study was to investigate the efficacy of globus pallidus interna deep brain stimulation (GPi-DBS) for treating dystonia due to the GNAL mutation. METHODS: We provide the first report of a dystonia patient with a genetically confirmed GNAL mutation in the Korean population and reviewed the literature on patients with the GNAL mutation who underwent GPi-DBS. We compared the effectiveness of DBS in patients with the GNAL mutation compared to that in patients with DYT1 and DYT6 in a previous study. RESULTS: Patients with the GNAL mutation and those with DYT1 had higher early responder rates (GNAL, 5/5, 100%; DYT1, 7/7, 100%) than did patients with DYT6 (p = 0.047). The responder rates at late follow-up did not differ statistically among the three groups (p = 0.278). The decrease in the dystonia motor scale score in the GNAL group was 46.9% at early follow-up and 63.4% at late follow-up. CONCLUSION: GPi-DBS would be an effective treatment option for dystonia patients with the GNAL mutation who are resistant to medication or botulinum toxin treatment.

Dramatic unilateral decrease in uptake via the dopamine transporter: Imaging in a patient with hemiparkinsonism following the lacunar stroke in substantia nigra

@#Vascular parkinsonism (VaP) is typically defined as having predominant lower body involvement, postural instability, less prominent rest tremor and little or no response to treatment with levodopa. In this study, we report a patient with VaP with clear demonstration of a dramatic unilateral decrease of radiotracer uptake in a 18F-FP-CIT-PET study. A 62-year-old right-handed woman was referred to the neurology department due to rest tremor and rigidity in the right hand, which began after undergoing resection surgery for a left acoustic neuroma 7 years prior. Brain MRI, taken at 1 year after surgery showed an ischemic stroke lesion in the left medial pons and the left substantia nigra. 18F-FP-CIT-PET revealed a marked reduction of radiotracer uptake in left striatum compared to that of the right. We treated the patient with 100 mg of levodopa, 200 mg of entacarpone and 25 mg of carbidopa. There was an improvement in bradykinesia and tremor, but the symptoms persisted, and there was no deterioration during 6 months of observation. After acoustic neuroma surgery, ischemic complications are uncommon, and even a small lesion in the nigrostriatal pathway can cause a hemiparkinsonism. If a patient experience sudden onset hemiparkinsonism, they should be carefully examined for lesions in the nigrostriatal pathways. Under these conditions, the 18F-FP-CIT-PET scan can enable visualization of a unilateral decrease and is a useful tool for diagnosis and differentiation from idiopathic Parkinson’s disease

Involuntary Flexor Spasms Associated with Basal Ganglia Infarction

Flexor spasm caused by stroke has been rarely reported. We describe a 79-year-old man who suddenly presented with flexor spasm of left limb and neck muscles. His symptoms consisted of recurrent episodes of brief paroxysmal flexor contractions of left limb and neck muscles without alteration of consciousness. Brain Magnetic Resonance Imaging revealed acute infarction in right basal ganglia. The abnormal movement was not associated with any epileptiform discharges in the video-electroencephalography monitoring. It was controlled with carbamazepine and phenytoin.

Diffusion Tensor Imaging Changes Correlate with Clinical Progression in Vascular Mild Cognitive Impairment and Vascular Dementia of Subcortical Type

BACKGROUND: Cerebral small vessel disease (SVD) induces vascular cognitive impairment (VCI) such as subcortical vascular dementia (SVaD) and subcortical vascular mild cognitive impairment (svMCI). We compared MRI parameters between SVaD and svMCI and determined which MRI parameters best correlated with cognitive function and disability on cross-sectional and longitudinal analyses within them. METHODS: Twenty-four patients with SVaD and twelve with svMCI were recruited. They underwent multimodal MRIs including fluid-attenuated inversion recovery lesion load, lacunar infarct number, and fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor imaging (DTI), neuropsychological testing, Sum of Boxes of Clinical Dementia Rating Scale (CDR-SB), Barthel Index, and the Korean version of a Geriatric Depression Scale (GDS-K). Seventeen patients were retested after 20 months for a brain MRI and clinical evaluation. RESULTS: There were significant differences in average MD and peak height of MD histograms within normal-appearing brain tissue (NABT) between SVaD and svMCI patients. In the cross-sectional analysis, average MD within NABT significantly correlated with the composite neuropsychology score (r=-0.80, p<0.001), the composite executive function score (r=-0.67, p< 0.001), and the CDR-SB (r=0.54, p=0.001), and the Barthel Index correlated with peak heights of the MD histograms (r=0.37, p=0.03) in NABT. Changes of CDR-SB was associated with changes of average MD within WMH (r=0.57, p=0.02), and changes of GDS-K was associated with changes of WMH volume (r=0.51, p=0.04) on a longitudinal scale. CONCLUSIONS: DTI parameters in NABT correlated with cognitive impairment and disability in VCI associated with SVD. Clinical progression of SVD was associated with some increment of WML volume and ultrastructural changes in WMH.