Parkinson's disease (PD) and multiple system atrophy (MSA) are neurodegenerative diseases representative of alpha-synucleinopathies characterized pathologically by alpha-synuclein-abundant Lewy bodies and glial cytoplasmic inclusions, respectively. Embryonic stem cells, fetal mesencephalic neurons, and neural stem cells have been introduced as restorative strategies in PD animals and patients, but ethical and immunological problems as well as the serious side effects of tumorigenesis and disabling dyskinesia have limited clinical application of these stem cells. Meanwhile, cell therapy using mesenchymal stem cells (MSCs) is attractive clinically because these cells are free from ethical and immunological problems. MSCs are present in adult bone marrow and represent <0.01% of all nucleated bone marrow cells. MSCs are themselves capable of multipotency, differentiating under appropriate conditions into chondrocytes, skeletal myocytes, and neurons. According to recent studies, the neuroprotective effect of MSCs is mediated by their ability to produce various trophic factors that contribute to functional recovery, neuronal cell survival, and stimulation of endogenous regeneration and by immunoregulatory properties that not only inhibit nearly all cells participating in the immune response cell-cell-contact-dependent mechanism, but also release various soluble factors associated with immunosuppressive activity. However, the use of MSCs as neuroprotectives in PD and MSA has seldom been studied. Here we comprehensively review recent advances in the therapeutic roles of MSCs in PD and MSA, especially focusing on their neuroprotective properties and use in disease-modifying therapeutic strategies.
Adult ; Animals ; Bone Marrow ; Bone Marrow Cells ; Cell Survival ; Cell Transformation, Neoplastic ; Chondrocytes ; Dyskinesias ; Embryonic Stem Cells ; Humans ; Inclusion Bodies ; Lewy Bodies ; Mesenchymal Stromal Cells ; Multiple System Atrophy ; Muscle Fibers, Skeletal ; Neural Stem Cells ; Neurodegenerative Diseases ; Neurons ; Neuroprotective Agents ; Parkinson Disease ; Regeneration ; Stem Cells ; Tissue Therapy

Subjective cognitive complaints (SCCs) refer to self-perceived cognitive decline and are related to objective cognitive decline. SCCs in cognitively normal individuals are considered a preclinical sign of subsequent cognitive impairment due to Alzheimer’s disease, and SCCs in cognitively normal patients with Parkinson’s disease (PD) are also gaining attention. The aim of this review was to provide an overview of the current research on SCCs in cognitively normal patients with PD. A systematic search found a lack of consistency in the methodologies used to define and measure SCCs. Although the association between SCCs and objective cognitive performance in cognitively normal patients with PD is controversial, SCCs appear to be predictive of subsequent cognitive decline. These findings support the clinical value of SCCs in cognitively normal status in PD; however, further convincing evidence from biomarker studies is needed to provide a pathophysiological basis for these findings. Additionally, a consensus on the definition and assessment of SCCs is needed for further investigations.

The concept of cognitive reserve (CR) in Alzheimer’s disease (AD) explains the differences between individuals in their susceptibility to AD-related pathologies. An enhanced CR may lead to less cognitive deficits despite severe pathological lesions. Parkinson’s disease (PD) is also a common neurodegenerative disease and is mainly characterized by motor dysfunction related to striatal dopaminergic depletion. The degree of motor deficits in PD is closely correlated to the degree of dopamine depletion; however, significant individual variations still exist. Therefore, we hypothesized that the presence of motor reserve (MR) in PD explains the individual differences in motor deficits despite similar levels of striatal dopamine depletion. Since 2015, we have performed a series of studies investigating MR in de novo patients with PD using the data of initial clinical presentation and dopamine transporter PET scan. In this review, we summarized the results of these published studies. In particular, some premorbid experiences (i.e., physical activity and education) and modifiable factors (i.e., body mass index and white matter hyperintensity on brain image studies) could modulate an individual’s capacity to tolerate PD pathology, which can be maintained throughout disease progression.

The ocular tilt reaction (OTR) represents a fundamental pattern of eye hand coordination in roll plane and consists of head tilt, conjugate eye torsion, hypotropia, all toward the same side. OTR can be observed not only in patients with peripheral vestibular dysfucntion but also in these with lesions of the graviceptive pathway, which runs from the vestibular nuclei, crossing the midline at the caudal pons, to the intersititial nucleus of Cajal in the rostral midbrain. We present two patients showed complete OTR with the caudal pontine lesions. The first patient was a 65-year-old woman and the lesions involved the dorsolateral portion of pontomedullary junction and cerebellum which was corn patible with AICA and PICA territorial infarction, a magnetic resonanse image(MRI). The ipsiversive OTR in the first patient might be secondary to the ipsilateral vestibular nuclear lesion. The second patient was a 60 year old man and revealed the infarctions in tegmental portion of caudal pons and cerebellum on MRI. The contraversive OTR in the second patient may be secondary to the pontine tegmental lesion involving medial longitudinal fasciculus which is a structure responsible for ascending crossed contralateral graviceptive pathway. OTR is a sensitive brainstem sign of lateralizing and localizing value and our presenting cases support that OTR represents vestibular tone imbalance in the graviceptive pathways.
Aged ; Brain Stem ; Cerebellum ; Female ; Hand ; Head ; Humans ; Infarction ; Magnetic Resonance Imaging ; Mesencephalon ; Middle Aged ; Pica ; Pons ; Vestibular Nuclei ; Zea mays

Recently with the development of magnetic resonance imaging(MRI) techniques, many reports of radiologic findings in spontaneous intracranial hypotension(SIH) have been reported. However in our review, the pachymeningeal changes within spinal canal secondary to SIH are not reported. In SIH, same mechanisms of it might act in the intraspinal space, which cause pachymeningeal changes of spinal dura and clinical features of spinal involvement. We reports four cases of SIH, in which MRI of the brain and spine reveals diffuse symmetric pachymeningeal enhancement. This is the first report of the spinal images in SIH.
Brain ; Intracranial Hypotension* ; Magnetic Resonance Imaging* ; Spinal Canal ; Spine

Background: It is important to make the accurate diagnosis of leptomeningeal metastasis(LM) because the institution of appropriate therapy may produce symptomatic improvement, prevent neurologic deterioration, and prolong survival. To evaluate the appropriate diagnostic methods of LM, we conducted the comparison of diagnostic yield in each diagnostic method and analyzed factors influencing the diagnostic results. METHODS: We analyzed 62 patients of LM with following inclusion criteria: positive CSF cytology, or abnormal neuroimaging, or elevated CSF biochemical marker, or characteristic clinical symptom and abnormal routine CSF examination. RESULTS: Primary cancer of LM was following; lung cancer 21, lymphoma 15, stomach cancer 13, breast cancer 9, rhabdomyosarcoma 2, bladder cancer 1, and colon cancer 1. The positive yield in the diagnosis of LM was 54.5% in CSF cytology, 55.9% in neuroimaging, 62.5% in CSF biochemical marker. As each diagnostic method was combined, the positive yield was increased to 86.4-88.5% with the highest in combination of CSF cytology with neuroimaging. The relationship between CSF cytology and neuroimaging is complementary in the diagnosis of LM (p=0.01). In positive group of CSF cytology, the count of CSF WBC was higher than in negative group (p=0.026), and clinical feature revealed a tendency of combined cerebral and cranial symptom than isolated symptom. The interval from the diagnosis of primary cancer to diagnosis of LM was most prolonged in breast cancer with a mean of 38.2 month. CONCLUSIONS: Combination of each diagnostic method increases the diagnostic yield, and CSF cytology and neuroimaging must be performed with each other.
Biomarkers* ; Breast Neoplasms ; Colonic Neoplasms ; Diagnosis ; Humans ; Lung Neoplasms ; Lymphoma ; Neoplasm Metastasis* ; Neuroimaging* ; Rhabdomyosarcoma, Alveolar ; Stomach Neoplasms ; Urinary Bladder Neoplasms

BACKGROUND: Pantothenate-kinase-associated neurodegeneration (PKAN) is an autosomal recessive neurodegenerative disorder that is characterized by progressive extrapyramidal signs, visual loss, and cognitive impairment. PKAN is caused by mutations in the pantothenate kinase gene (PANK2), which is located on chromosome 20p13 and encodes pantothenate kinase, the key regulatory enzyme in coenzyme-A biosynthesis. CASE REPORT: In this report we describe a case of atypical PKAN with a novel PANK2 mutation, presenting with a 10-year history of postural tremor involving both hands. Upon neurological examination, the patient's face was masked and he spoke in a monotonous voice. The patient presented with mild bradykinesia and rigidity that involved all of the extremities. Horizontal saccadic eye movements were slow and fragmented. Brain MRI revealed a typical "eye-of-the-tiger" sign. A mutation analysis revealed three PANK2 mutations: two in exon 3 (Asp 378Gly and Leu385CysfsX13) and one in exon 4 (Arg440Pro). CONCLUSIONS: Parkinsonism is not an unusual presenting symptom in patients with atypical PKAN, and so it is important for physicians to consider PKAN in the differential diagnosis of patients presenting with young-onset parkinsonism.
Brain ; Diagnosis, Differential ; Exons ; Extremities ; Hand ; Humans ; Hypokinesia ; Masks ; Neurodegenerative Diseases ; Neurologic Examination ; Parkinsonian Disorders ; Phosphotransferases ; Phosphotransferases (Alcohol Group Acceptor) ; Saccades ; Tremor ; Voice

With the development of electrophysiologic technique, a more detailed topographical organizations of motor cortex, especially hand area have been introduced in animal experiment. To the best our knowledge, in cerebral infarction, only one patient with isolated weakness of intrinsic hand muscles has been reported. We present two patients with cerebral infarction who showed isolated weakness in their intrinsic hand. Patient 1; A 76-year-old woman with coronary artery obstructive disease developed abrupt weakness in flexion of right thumb, index, middle finger and in adduction of thumb. Brain MRI showed a small discrete lesion in the posterior bank of left precentral gyrus. An angiography revealed an occlusion of left central sulcus artery. Prominent thumb adduction weakness was remained 11 days later. Patient 2; A 57-year-old hypertensive man was admitted because of recurrent TIA and decreased grasp power of right hand, especially flexion and adduction of thumb, index finger and middle finger. Brain MRI showed focal lamina necrosis in left precentral gyrus. An angiography revealed an occlusion of left internal carotid artery. Findings in our patients suggest that the similar arrangement of efferent zone for cortical hand area found in monkeys also may exist in human beings.
Aged ; Angiography ; Animal Experimentation ; Arteries ; Brain ; Carotid Artery, Internal ; Cerebral Infarction ; Coronary Vessels ; Female ; Fingers ; Hand Strength ; Hand* ; Haplorhini ; Humans ; Infarction* ; Magnetic Resonance Imaging ; Middle Aged ; Motor Cortex ; Muscles* ; Necrosis ; Thumb

It is difficult to determine the pathoanatomical correlates of dystonia because of its complex pathophysiology, and most cases with secondary dystonia are associated with basal ganglia lesions. Moreover, it is a challenging issue that patients with abnormal postures accompanied by other neurological findings in the affected body part (e.g., sensory loss) can be diagnosed with true dystonia or pseudodystonia. Here, we report a case of abnormal postures with loss of proprioception in the left extremities after right dorsal pontine hemorrhage.

Multiple-system atrophy (MSA) is an adult-onset, sporadic, progressive neurodegenerative disease. Clinically, the cardinal features include autonomic failure, parkinsonism, cerebellar ataxia, and pyramidal signs in any combination, of which autonomic failure is an integral component in the diagnosis. Pathologically, MSA is characterized by alpha-synuclein-positive glial cytoplasmic inclusions and neuronal loss, predominantly in the basal ganglia, brainstem, cerebellum, and intermediolateral cell columns of the spinal cord. We report the first case of MSA confirmed by autopsy in Korea.
Atrophy ; Autopsy ; Basal Ganglia ; Brain Stem ; Cerebellar Ataxia ; Cerebellum ; Inclusion Bodies ; Korea ; Multiple System Atrophy ; Neurodegenerative Diseases ; Neurons ; Parkinsonian Disorders ; Spinal Cord