Na-Yeon Jung

Pure upbeat nystagmus in association with bilateral internuclear ophthalmoplegia

A 66-year-old man developed primary position upbeat nystagmus and bilateral internuclear ophthalmoplegia (INO). Video-oculography showed primary position upbeat nystagmus with exponentially decreasing slow phases, which disappeared in darkness. Brain MRI disclosed enhancing lesions involving bilateral dorsomedial pons extending from the middle to upper portion. Upbeat nystagmus in association with bilateral INO may be attributed by the damage of the cell groups of the paramedian tracts (PMT), the projections from the interstitial nucleus of Cajal (INC) to PMT, or the connections between INC and the nucleus of Roller.

Secondary tics after osmotic demyelination syndrome involving both the striatum and the cerebral cortex

Although some reports have associated parkinsonism, dystonia, and chorea with the extrapontine lesions of osmotic demyelination syndrome (ODS), to our knowledge delayed-onset tic disorder has not been reported. Thus, we report a rare secondary tic associated with ODS involving both the striatum and the cerebral cortex. We can hypothesize that aberrant neuronal plasticity after the initial insult in both basal ganglia and motor cortical areas could be implicated in the pathogenesis of delayed-onset tics.

An autopsy confirmed case of progressive supranuclear palsy with predominant cerebellar ataxia

Progressive supranuclear palsy (PSP) is characterized by early appearance of postural instability and supranuclear gaze palsy [1]. However, considerable clinical variability has been reported, such as Richardson’s syndrome, PSPparkinsonism, PSP-pure akinesia with gait freezing, behavioral variant frontotemporal dementia, and non-fluent/agrammatic variant primary progressive aphasia [1]. Kanazawa et al. recently defined a new clinical subtype of PSP with cerebellar ataxia as the initial and prominent symptom, called PSP with predominant cerebellar ataxia (PSP-C) [2]. Here, we present our observation of a pathologically confirmed PSP-C patient, who was initially diagnosed with multiple system atrophy-cerebellar type (MSA-C). A 64-year-old man had been referred to our hospital for frequent falls and disequilibrium. His symptoms started with orthostatic dizziness and gait unsteadiness at the age of 59. Dysarthria, hitting and kicking his wife during sleep, severe snoring, dysphagia, and urinary frequency had developed over the last 4 years. He had also become emotionally labile at approximately the same time. At the age of 64, his postural instability had become more apparent and he had frequently fallen backward when standing without assistance. He had been treated for Gi Yeong Huh, Eun-Joo Kim contribute equally.

Mild Clinical Features and Histopathologically Atypical Cores in Two Korean Families with Central Core Disease Harboring RYR1 Mutations at the C-Terminal Region

Background Central core disease (CCD) is a congenital myopathy characterized by distinctive cores in muscle fibers. Mutations in the gene encoding ryanodine receptor 1 (RYR1) have been identified in most CCD patients. Case Report Two unrelated patients presented with slowly progressive or nonprogressive proximal muscle weakness since childhood. Their family history revealed some members with the same clinical problem. Histological analysis of muscle biopsy samples revealed numerous peripheral cores in the muscle fibers. RYR1 sequence analysis disclosed a novel mutation in exon 101 (c.14590T>C) and confirmed a previously reported mutation in exon 102 (c.14678G>A). Conclusions We report herein two families with CCD in whom missense mutations at the C-terminal of RYR1 were identified. Although it has been accepted that such mutations are usually associated with a severe clinical phenotype and clearly demarcated central cores, our patients exhibited a mild clinical phenotype without facial muscle involvement and skeletal deformities, and atypical cores in their muscle biopsy specimens.

A case of parakinesia brachialis oscitans

There have been few described cases of hemiplegia with involntary elevation of paralyzed arms while yawning, symptoms eferred to as parakinesia brachialis oscitans [1–4]. Brain imagng shows that lesions in the internal capsule or basal ganglia are ainly associated with this movement [1–4]. We report a patient f parakinesia brachialis oscitans after acute infarction involving he right motor cortex and frontal subcortex.

Longitudinal outcomes of amyloid positive versus negative amnestic mild cognitive impairments: a three-year longitudinal study

We aimed to compare the longitudinal outcome of amnestic mild cognitive impairment (aMCI) patients with significant Pittsburgh Compound B uptake [PiB(+) aMCI] and those without [PiB(−) aMCI]. Cerebral β-amyloid was measured in 47 patients with aMCI using PiB-positron emission tomography (PET) (31 PiB(+) aMCI and 16 PiB(−) aMCI). Clinical (Nu2009=u200947) and neuropsychological follow-up (Nu2009=u200937), and follow-up with brain magnetic resonance imaging (Nu2009=u200938) and PiB-PET (Nu2009=u200930) were performed for three years. PiB(+) aMCI had a higher risk of progression to dementia (hazard ratiou2009=u20093.74, 95% CIu2009=u20091.21–11.58) and faster rate of cortical thinning in the bilateral precuneus and right medial and lateral temporal cortices compared to PiB(−) aMCI. Among six PiB(−) aMCI patients who had regional PiB uptake ratio >1.5 in the posterior cingulate cortex (PCC), three (50.0%) progressed to dementia, and two of them had global PiB uptake ratio >1.5 at the follow-up PiB-PET. Our findings suggest that amyloid imaging is important for predicting the prognosis of aMCI patients, and that it is necessary to pay more attention to PiB(−) aMCI with increased regional PiB uptake in the PCC.

Early stage memory impairment, visual hallucinations, and myoclonus combined with temporal lobe atrophy predict Alzheimer’s disease pathology in corticobasal syndrome

ABSTRACT Corticobasal syndrome (CBS) is a typical phenotype of corticobasal degeneration (CBD). However, autopsy series have shown that many CBS cases emerge from various types of non-CBD pathology. We report a 73-year-old Korean man who was clinically diagnosed with CBS whose underlying pathology was Alzheimer’s disease (AD) at autopsy (CBS-AD). This case suggests that early developing memory impairment and myoclonus, severe temporoparietal atrophy, and visual hallucinations may support a more specific prediction of CBS-AD.

Analysis of frontotemporal dementia, amyotrophic lateral sclerosis, and other dementia-related genes in 107 Korean patients with frontotemporal dementia

To identify pathogenic variants in 107 Korean patients with sporadic frontotemporal dementia (FTD), 46 genes related to FTD, amyotrophic lateral sclerosis, and other dementias were screened by next-generation sequencing. Hexanucleotide repeats in C9orf72 gene were also tested by repeat-primed polymerase chain reaction. Next-generation sequencing revealed one known pathogenic variant (c.708+1G>A) in the GRN gene in a patient with behavioral variant FTD (bvFTD). In addition, a novel in-frame deletion (c.2675_2683del) in the CSF1R gene was identified in a patient with bvFTD who had severe bifrontal atrophy with frontal subcortical white matter changes. Novel compound heterozygous variants in the AARS2 gene, c.1040+1G>A and c.636G>A (p.Met212Ile), were found in a patient with bvFTD. Forty-six variants of uncertain significance were detected in other patients. None of the patients had expanded hexanucleotide repeats in C9orf72. These results show that pathogenic variants of known FTD genes are rare in Korean FTD patients but the CSF1R and AARS2 genes should be screened for a genetic diagnosis of FTD or other dementias.

G.P.67 Favorable response to low dose oral methotrexate in acute sarcoid myositis

Abstract Sarcoidosis is a multisystemic granulomatous disease of unknown etiology. Diagnosis depends on clinico-radiologic features, histologic proof of non-caseating granulomas, and exclusion of other granulomatous diseases. Patients commonly present with bilateral hilar lymphadenopathy, pulmonary infiltrates, and ocular and skin lesions. Asymptomatic muscle involvement with systemic sarcoidosis occurs in 50–80% of patients, while symptomatic myositis, mostly as chronic form, is in less than 3%. Acute myopathy as an initial manifestation is extremely rare. We recently experienced a rapidly progressive case of acute sarcoid myositis, which showed a favorable response to low dose of oral methotrexate. A 49-year-old woman was admitted with progressive limb weakness for 2xa0months. Her symptom began with difficulties in climbing stairs. Her weakness extended to arm and neck in 1xa0month. She reported weight loss and mild dyspnea over months. Her weakness was on proximal arms and legs, showing waddling gait and Gower’s sign. Serum angiotensin-converting enzyme and creatine kinase level was elevated; ESR and CRP were also slight elevated. Needle electromyography showed active myopathic patterns. Muscle biopsy disclosed many non-caseating granulomas and some lymphohistiocytic infiltaration in perimysial space together with multiple necrotic and regenerating fibers. A systemic search for granuloma revealed bilateral hilar and mediastinal lymphnode enlargement on chest computed tomography and whole-body fluorodeoxyglucose positron emission tomography. Corticosteroid therapy is considered the mainstay of treatment for sarcoid myopathy. However, weakness got worse in this case, despite high-dose methylprednisolone followed by oral prednisolone. We added 15xa0mg/week of oral methotrexate and finally she began to improve slowly with notable improvement in her muscle strength. We recommend methotrexate as an effective second-line treatment option in patients with acute sarcoid myositis.

G.P.45 A family of autosomal dominant limb-girdle muscular dystrophy with rimmed vacuole

Abstract Limb-girdle muscular dystrophy (LGMD) is a descriptive term that encompasses childhood- or adult-onset muscular dystrophies, not characterized as dystrophinopathy. While most cases of LGMD follow autosomal recessive inheritance, many families with distinct autosomal dominant (AD) pattern have been reported. Causative genes are known for three of the AD LGMDs, which are myotilin, lamin A/C, and caveolin-3. For the other AD LGMDs, loci by linkage analysis are identified. We found a family of AD LGMD. The affected are 11, both male and female, out of 37 family members through three successive generations without consanguineous marriage. Limb weakness typically starts during childhood. The affected has never been good at sports. They have difficulty lifting heavy objects or climbing stairs, after which pain follows in the used limbs. On examination, mild proximal limb muscle atrophy was noted with moderate calf pseudohypertrophy. Contracture was not evident. They showed Gower’s sign and waddling gait. Distal muscle power was largely preserved compared to proximal parts. Most interestingly, all of the affected had dysphagia that it was a rule to assume chin tuck posture on swallowing. They also had nasal voice with drooping soft palate, but did not have other difficulty in articulation. On muscle biopsy, scattered rimmed vacuoles were noted upon general dystrophic features. Immunohistochemistry of dystrophin, sarcoglycans, dysferlin, and dystroglycans did not reveal abnormality. Distinctive clinical features of previously characterized LGMD like contracture or mounding do not match with this family. Based upon inheritance pattern and pathologic finding, we sequenced myotilin (TTID), but failed to prove any mutation. Very likely this family with unique clinical/pathologic features are due to mutation in a novel gene. Extensive search for the causative gene including exome sequencing and/or linkage analysis is warranted for genetic diagnosis and therapeutic opportunities.