Mutations in the F-box only protein 7 (FBXO7) gene are the cause of autosomal recessive parkinsonian-pyramidal syndrome. Herein, we report a patient with a novel FBXO7 mutation with a unique clinical presentation. A 43-year-old male visited our hospital with complaints of progressing gait disturbance since a generalized tonic clonic seizure. There were no past neurological symptoms or familial disorders. Neurological examination revealed bradykinesia, masked face, stooped posture, parkinsonian gait, and postural instability. The bilateral uptake by dopamine transporters was nearly abolished, as determined by N-(3-[18F]fluoropropyl)- 2β-carbon ethoxy-3β-(4-iodophenyl) nortropane positron emission tomography (18F-FP-CIT PET). Next-generation sequencing revealed a heterozygous c.1066_1069delTCTG (p.Ser356ArgfsTer56) frameshift variant and a heterozygous c.80G>A (p.Arg27His) missense variant of the FBXO7 gene. The patient’s specific clinical features, medication-refractory parkinsonism and seizures further broaden the spectrum of FBXO7 mutations. The nearly abolished dopamine transporter uptake identified by 18F-FP-CIT PET is frequently found in patients with FBXO7 mutations, which is different from the usual rostrocaudal gradient that is observed in patients with Parkinson’s disease.

Alternating hemiplegia of childhood (AHC) is a rare neurodevelopmental disorder characterized by recurrent paroxysmal hemiplegic attacks that affect one or the other side of the body. Up to 74% of patients with AHC have a pathologic variant in the ATP1A3 gene. After the introduction of next-generation sequencing, intermediate cases and atypical cases have expanded the clinical spectrum of ATP1A3-related disorders. Herein, we report the first case of AHC in Korea. A 33-year-old man visited our hospital with recurrent hemiplegic and dystonic episode after his first birthday. He was completely normal between episodes and did not have any ataxia, but brain magnetic resonance imaging showed cerebellar atrophy. He also had pes planovalgus deformity. Whole exome sequencing revealed a heterozygous G947R variant in the ATP1A3 gene (c.2839G > C, rs398122887), which is a known pathologic variant. This atypical case of AHC demonstrates the importance of the clinical approach in diagnosing ATP1A3-related disorders.

BACKGROUND: Quantitative susceptibility mapping (QSM) has been used to measure iron accumulation in the deep nuclei of patients with Parkinson's disease (PD). This study examined the relationship between non-motor symptoms (NMSs) and iron accumulation in the deep nuclei of patients with PD. METHODS: The QSM data were acquired from 3-Tesla magnetic resonance imaging (MRI) in 29 patients with early PD and 19 normal controls. The Korean version of the NMS scale (K-NMSS) was used for evaluation of NMSs in patients. The patients were divided into high NMS and low NMS groups. The region-of-interest analyses were performed in the following deep nuclei: red nucleus, substantia nigra pars compacta, substantia nigra pars reticulata, dentate nucleus, globus pallidus, putamen, and head of the caudate nucleus. RESULTS: Thirteen patients had high NMS scores (total K-NMSS score, mean = 32.1), and 16 had low NMS scores (10.6). The QSM values in the deep were not different among the patients with high NMS scores, low NMS scores, and controls. The QSM values were not correlated linearly with K-NMSS total score after adjusting the age at acquisition of brain MRI. CONCLUSION: The study demonstrated that the NMS burdens are not associated with iron accumulation in the deep nuclei of patients with PD. These results suggest that future neuroimaging studies on the pathology of NMSs in PD should use more specific and detailed clinical tools and recruit PD patients with severe NMSs.
Basal Ganglia ; Brain ; Caudate Nucleus ; Cerebellar Nuclei ; Globus Pallidus ; Head ; Humans ; Iron* ; Magnetic Resonance Imaging ; Neuroimaging ; Parkinson Disease* ; Pars Compacta ; Pars Reticulata ; Pathology ; Putamen ; Red Nucleus

Objective: Orthostatic hypotension (OH) is one of the most common autonomic dysfunctions in Parkinson’s disease (PD) patients. However, many patients with OH are asymptomatic. Conversely, orthostatic dizziness (OD) is not always associated with OH. We investigated the effects of positional changes on cerebral perfusion in patients with PD and OH. Methods: We enrolled 42 patients, comprising 31 PD patients and 11 healthy controls. All the subjects underwent the following clinical assessments: the OH questionnaire, head-up tilt test (HUTT) with transcranial Doppler (TCD), near-infrared spectroscopy, measurement of the change in oxygenated hemoglobin (ΔHboxy) during the squat-to-stand test (SST), measurement of the time derivative of total hemoglobin (DHbtot), and time taken to reach the peak (peak time [PT]) of DHbtot after restanding. Results: The mean flow velocity change (ΔMFV) in the TCD during the HUTT failed to differentiate between the PD-OH(+) and PD-OH(-) groups. The change in oxygenated hemoglobin ΔHboxy was greater in the PD-OH(+) group, which persisted for 9 min until the end of the HUTT only in the left hemisphere. During SST, PT was significantly delayed in the left hemisphere in PD-OH(+) patients. Conclusion Although TCD demonstrated no significant difference in ΔMFV, the parameters measured by near-infrared spectroscopy, such as ΔHboxy during HUTT and PT during the SST, significantly increased ΔHboxy or delayed PT in the left hemisphere of PD-OH(+). Positional changes have a detrimental effect on cerebral hemodynamics in patients with PD and OH, especially in the left hemisphere.

Objective: Orthostatic hypotension (OH) is one of the most common autonomic dysfunctions in Parkinson’s disease (PD) patients. However, many patients with OH are asymptomatic. Conversely, orthostatic dizziness (OD) is not always associated with OH. We investigated the effects of positional changes on cerebral perfusion in patients with PD and OH. Methods: We enrolled 42 patients, comprising 31 PD patients and 11 healthy controls. All the subjects underwent the following clinical assessments: the OH questionnaire, head-up tilt test (HUTT) with transcranial Doppler (TCD), near-infrared spectroscopy, measurement of the change in oxygenated hemoglobin (ΔHboxy) during the squat-to-stand test (SST), measurement of the time derivative of total hemoglobin (DHbtot), and time taken to reach the peak (peak time [PT]) of DHbtot after restanding. Results: The mean flow velocity change (ΔMFV) in the TCD during the HUTT failed to differentiate between the PD-OH(+) and PD-OH(-) groups. The change in oxygenated hemoglobin ΔHboxy was greater in the PD-OH(+) group, which persisted for 9 min until the end of the HUTT only in the left hemisphere. During SST, PT was significantly delayed in the left hemisphere in PD-OH(+) patients. Conclusion Although TCD demonstrated no significant difference in ΔMFV, the parameters measured by near-infrared spectroscopy, such as ΔHboxy during HUTT and PT during the SST, significantly increased ΔHboxy or delayed PT in the left hemisphere of PD-OH(+). Positional changes have a detrimental effect on cerebral hemodynamics in patients with PD and OH, especially in the left hemisphere.