Urinary Biomarkers for Neurodegenerative Diseases

Global incidence of neurodegenerative diseases (NDDs) such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) is rapidly increasing, but the diagnosis of these diseases at their early stage is challenging. Therefore, the availability of reproducible and reliable biomarkers to diagnose such diseases is more critical than ever. In addition, biomarkers could be used not only to diagnose diseases but also to monitor the development of disease therapeutics. Urine is an excellent biofluid that can be utilized as a source of biomarker to diagnose not only several renal diseases but also other diseases because of its abundance in invasive sampling. However, urine was conventionally regarded as inappropriate as a source of biomarker for neurodegenerative diseases because it is anatomically distant from the central nervous system (CNS), a major pathologic site of NDD, in comparison to other biofluids such as cerebrospinal fluid (CSF) and plasma. However, recent studies have suggested that urine could be utilized as a source of NDD biomarker if an appropriate marker is predetermined by metabolomic and proteomic approaches in urine and other samples. In this review, we summarize such studies related to NDD.

Inhibition of beta-amyloid(1-40) Peptide Aggregation and Neurotoxicity by Citrate

The accumulation of beta-amyloid (A beta) aggregates is a characteristic of Alzheimer's disease (AD). Furthermore, these aggregates have neurotoxic effects on cells, and thus, molecules that inhibit A beta aggregate formation could be valuable therapeutics for AD. It is well known that aggregation of A beta depends on its hydrophobicity, and thus, in order to increase the hydrophilicity of A beta, we considered using citrate, an anionic surfactant with three carboxylic acid groups. We hypothesized that citrate could reduce hydrophobicity and increase hydrophilicity of A beta(1-40) molecules via hydrophilic/electrostatic interactions. We found that citrate significantly inhibited A beta(1-40) aggregation and significantly protected SH-SY5Y cell line against A beta(1-40) aggregates-induced neurotoxicity. In details, we examined the effects of citrate on A beta(1-40) aggregation and on A beta(1-40) aggregates-induced cytotoxicity, cell viability, and apoptosis. Th-T assays showed that citrate significantly inhibited A beta(1-40) aggregation in a concentration-dependent manner (Th-T intensity: from 91.3% in 0.01 mM citrate to 82.1% in 1.0 mM citrate vs. 100.0% in A beta(1-40) alone). In cytotoxicity and viability assays, citrate reduced the toxicity of A beta(1-40) in a concentration-dependent manner, in which the cytotoxicity decreased from 107.5 to 102.3% as compared with A beta(1-40) aggregates alone treated cells (127.3%) and the cell viability increased from 84.6 to 93.8% as compared with the A beta(1-40) aggregates alone treated cells (65.3%). Furthermore, Hoechst 33342 staining showed that citrate (1.0 mM) suppressed A beta(1-40) aggregates-induced apoptosis in the cells. This study suggests that citrate can inhibit A beta(1-40) aggregation and protect neurons from the apoptotic effects of A beta(1-40) aggregates. Accordingly, our findings suggest that citrate administration should be viewed as a novel neuroprotective strategy for AD.

Type 1 Chiari Malformation Presenting With Medullary Infarction and Syncope

No abstract available.

Reversible Pontine MRI Lesion in Acute Thalamic Infarct: Reversible Encephalopathy due to Hypertension?

Posterior reversible encephalopathy syndrome associated with hypertension rarely presents with predominant involvement of the brainstem and is relative sparing of the supratentorial regions. A relative paucity of brainstem signs and symptoms, despite extensive neuroimaging abnormalities therein, support the diagnosis. Although elevation of blood pressure is common in acute cerebral infarction, concomitant brainstem edema has not been reported. We describe here the clinical and neuroimaging features of an unusual brainstem hyperintensity associated with acute ischemic stroke. The neuroimaging abnormalities improved after stabilization of blood pressure, distinguishing this syndrome from brainstem infarction.

Reversible Pontine MRI Lesion in Acute Thalamic Infarct: Reversible Encephalopathy due to Hypertension?

Posterior reversible encephalopathy syndrome associated with hypertension rarely presents with predominant involvement of the brainstem and is relative sparing of the supratentorial regions. A relative paucity of brainstem signs and symptoms, despite extensive neuroimaging abnormalities therein, support the diagnosis. Although elevation of blood pressure is common in acute cerebral infarction, concomitant brainstem edema has not been reported. We describe here the clinical and neuroimaging features of an unusual brainstem hyperintensity associated with acute ischemic stroke. The neuroimaging abnormalities improved after stabilization of blood pressure, distinguishing this syndrome from brainstem infarction.

Simultaneous Insonation of One MCA through Bilateral Temporal Bone Windows Using M-mode TCD

BACKGROUND: Transcranial Doppler ultrasonography (TCD) is limited by insufficient ultrasound penetration through the temporal bone. Recent studies have revealed poor temporal bone windows in 5~30% of patients. In about 38% of the patients with poor temporal bone windows, a temporal window was unilaterally absent. The aim of the present study was to compare the mean flow velocities (MFV) of the middle cerebral arteries (MCA) obtained through the ipsilateral temporal bone window with those obtained through the contralateral one using M-mode TCD. METHODS: Eighteen patients (mean age, 28 y; age range, 21~40 y) who had adequate bilateral temporal bone windows were enrolled and 36 MCAs were investigated. The investigators tried to detect the MCA through the ipsilateral and contralateral temporal windows with two 2-MHz probes simultaneously (ipsilateral insonation and contralateral one, respectively). RESULTS: The MCA MFV measured by ipsilateral insonation was 72.58 +/- 9.78 cm/sec and that demonstrated by contralateral insonation was 70.94 +/- 9.79 cm/sec. Even though the differences between MFVs by either side insonation was 2.25~3.94% (0~13.11%) and had significant difference statistically, those were within side-to-side limit of 30% generally considered as abnormal. The mean bitemporal diameter (BTD) was 130.72 +/- 3.75 cm (126~142 cm). We obtained similar waveforms in the reverse direction to those of ipsilateral insonation at 95.33 +/- 5.19 mm of depths (72.97 +/- 4.23% of BTD) during contralateral insonation. CONCLUSIONS: The demonstration of the MCA through the contralateral insonation provides an opportunity to obtain significant mean flow velocities in patients with absent or insufficient temporal bone window unilaterally.

Aseptic Meningitis in Kikuchi's Disease

The involvement of the nervous system in Kikuchi's disease (KD) is rare. Although some reports of meningeal involvement in KD were described in the literature from Japan, it has rarely been reported in Korea. A 23-year-old man presented with severe headache, fever, and vomiting. Cerebrospinal fluid (CSF) analysis revealed an opening pressure 300 mmH2O, WBC 283/mm3, glucose 44 mg/dl and protein 86 mg/dl. Multiple tender lymph nodes on the left anterior neck were found on the 9th day of his hospital stay. The lymph node biopsy disclosed histopathologic features typical of KD. We report a patient with KD accompanied by aseptic meningitis, emphasizing the importance of recognizing this disorder in diagnosing patients with meningitis.

A Case of Reversible Marchiafava-Bignami Disease Showing Severe Thalamic Hypometabolism in PET

No abstract available.

Family Caregiver's Burden of Stroke Patients

BACKGROUND: The role of family caregivers is becoming more important for the recovery of patients with stroke, as the prevalence of stroke is increasing. Consequently, the burden of caregiving can affect both patients' and caregiver's functional health. The purpose of this study was to make a novel caregiving burden scale and evaluate factors that influence the burden of the family caregiver. METHODS: The caregiver burden scale consists of four aspects: psycho-emotional, financial, physical and isolation from social activities. The questionnaire was administrated to the family care-givers of 118 patients with stroke who consented to be interviewed. Among 118 caregivers, we analyzed 106 caregivers who answered the questionnaire completely. We evaluated the construct validity and internal reliability of the burden scale and applied multiple regression analysis for the factors that influence caregiver's burden. RESULTS:1) Construct validity by factor analysis and Internal reliability was high 2) Among 106 caregivers, 40 (37.7%) approached subjective depression on the Beck Depression Inventory (BDI). There was a statistically significant difference(p<0.01) in the strength of burden between the groups with and without depression. 3)Of the variables, including patient's age, caregiver's age, duration of caregiving, education level of caregiver, and socio-economic status of family, only the BDI scores of caregivers and the Barthel Index scores of patients were correlated to the degree of caregiving burden. CONCLUSIONS: This caregiving burden scale can be a useful tool for the evaluation of caregiver's burden with stroke. We believe that thoughtful consideration and realistic support for family caregivers can be very important in the long-term management of patients with stroke. (J Korean Neurol Assoc 19(3):213~218, 2001)

Spontaneous Resolution of Spinal Epidural Hematoma

Spontaneous spinal epidural hematoma is an uncommon cause of acute non-traumatic myelopathy and usually requires surgical evacuation. The typical clinical presentation is that of sudden and severe neck or back pain followed by progressive motor, sensory, and sphincteric disturbances within minutes to hours. Although many cases are idio-pathic, common causes include anticoagulant therapy, coagulopathies, hypertension, and vascular malformations. Magnetic resonance imaging (MRI) has become the primary method for diagnosis and follow-up. Prompt neurosurgical treatment with decompressive laminectomy has been regarded as the general method for neurological recovery, although rare cases of spontaneous recovery have been reported. We report such a case of spontaneous cervical spinal epidural hematoma that showed complete spontaneous resolution.

Usefulness of Occipital EEG Spectral Profile in the Differential Diagnosis of Alzheimer Type and Vascular Dementia

BACKGROUND: Alzhiemeranjx disease (AD) and vascular dementia (VD) are common types of dementia. As a result of the development of new specific agents for AD, and because vascular dementia is a potentially preventable dementia, differentiating these diseases is of great importance. The role of EEG spectral analysis in the differential diagnosis between Alzheimer type and vascular dementia is still controversial. Since there have been few studies concerning the differential diagnosis of dementia by EEG, the present study has focused on this aspect. Usefulness of EEG in differen-tial diagnosis of dementia will be elucidated by clarifying relationship between type of dementia and spectral profile of EEG. METHODS: We analyzed the power spectra taken from 16 derivations and spectral profile was constructed by averaging twenty 2 sec epochs in three study groups (normal controls, AD and VD). Spectral profile was divided into three groups; (I) type A, showing a dominant 6.5-12 Hz peak (ii) type B, lacking a dominant peak in the 6.5-12 Hz (iii) type C, corresponding to a flat, low voltage, spectrum. To elucidate the relationship between spectral profile and other factors including diagnosis, statistical test was done. RESULTS: (1) In AD, type C profile was statistically more prevalent than in VD and type A profile was reversed. (2) In AD, Mini-Mental State Examination (MMSE) score was statistically lower in type C profile. (3) Spectral profile was not associated with age, age of symptom onset, and symptom duration. CONCLUSIONS: This study suggested that spectral profile is a useful tool for the differential diagnosis of dementia (AD and VD) and correlated with the severity of disease in AD.

A Case of Midbrain Hemorrhage Presenting as Bilateral Ptosis with Diurnal Fluctuation

A 54 year-old woman presented with bilateral fatigable blepharoptosis with diurnal fluctuation and diplopia for 10 days. She had a 3 year history of hypertension and showed symptoms of bilateral ptosis, supranuclear upward gaze palsy, and vertical diplopia with the pupils promptly constricting to light. Bell's phenomenon and vertical oculocephalic responses were intact but an impaired convergence was noted in both eyes. A intramuscular neostigmine test was negative. T1 and T2-wighted MRI of the brain showed a small round high signal intensity lesion in the periaqueductal gray (PAG) region. Therefore, she was diagnosed with a midbrain ptosis due to midbrain hemorrhage. The PAG lesion was suggested as contributing to the fatigable blepharoptosis and supranuclear upward gaze palsy in the patient. We recommend that patients with clinical features of myasthenia limited to the ocular muscles and, having risk factors for cerebrovascular disease, be thoroughly evaluated for intracranial lesions if warranted.

Clinical Characteristics of Geriatric Patients Admitted to Yongin Hyoja Geriatric Hospital

BACKGROUND: As the size of the elderly population has increased compared to the hole, there has been growing concern over potential health problems and geriatric hospitals for elderly people. However, despite the emerging needs for geriatric hospitals, there is no data on the clinical characteristics of patients being admitted to geriatric hospitals. To analyze the characteristics of elderly patients admitted to a geriatric hospital, we studied the medical records of patients admitted to Yong-in Hyoja Geriatric Hospital during a recent 20 months period. By clarifying the clinical characteristics of elderly patients admitted to a geriatric hospital, the basic data for understanding and treating elderly patients could be made. METHODS: We analyzed the medical records of 345 patients who were admitted to Yong-in Hyoja Geriatric Hospital from November 1997 to July 1999. The diagnosis of patients was largely subgrouped according to the existence of dementia, and subsequent detailed diagnoses were made. RESULTS: (1) The average age of patients was 74.59 years and there were slightly more females than males admitted (ratio, 1.15:1). (2) Most of the patients suffered from dementia (62.1%), of which vascular dementia was the most common(31.6%), followed by Alzheimer dementia(19.15%). (3) Compared to vascular dementia, patients with Alzheimer dementia had more severe cognitive dysfunction, psychosis, and agitation, while patients with vascular dementia had more problems in activities of daily living (ADL) and were more depressed than Alzheimer dementia (4) The average hospitalization duration was 3.54 months and incidence of significant illness after admission was 29.8%. The mortality rate was 10.9%. (5) The most common cause of death was infection (45.2%), followed by cardiovascular problems(16.2%). CONCLUSIONS: In addition to significant illnesses and mortality after admission, most patients admitted to geriatric hospitals have severe cognitive and behavioral problems. Therefore, adequate medical and neurological assessment and treatment for the aged is necessary.

A Case of Cerebral Infarction and Chronic Subdural Hematoma in Essential Thrombocythemia

Essential thrombocythemia is one type of the related chronic myeloproliferative disorders that also include poly-cythemia vera, chronic myelogenous leukemia, and idiopathic myelofibrosis. It is a rare disorder of unknown origin characterized by thrombocytosis, excessive megakaryocytes, hemorrhage, and thrombotic complication. Several cases of ischemic stroke in essential thrombocythemia have been reported, but cerebral infarction combined with cerebral hemorrhage has been very rare and has not been reported in Korea. We report a case of cerebral infarction and chronic subdural hematoma in a pateint with essential thrombocythemia. A 59-year-old woman with essential thrombocythemia was admitted with mild left hemiparesis that developed 3 days prior. She had a history of minor trauma 15 days prior. A brain MRI showed an infarction in the right temporal lobe and a chronic subdural hematoma in the right frontoparietal area. A cerebral angiography revealed an occlusion of the M2 portion of the right middle cerebral artery.

Congenital insensitivity to pain and anhidrosis with selective loss of unmyelinated fiber (Hereditory sensory autonomic neuropathy IV)

Hereditory Sensory Autonomic Neuropathy(HSAN) is variable rare disorder. So the classification of HSAN could be somewhat unsettled. There are intermingled overlap variants of HSAN in view of clinical manifestations and pathologic findings. Five types of HSAN have been described by Dyck(1993). Type I is dominantly inherited and affects both myelinated(MFs) and unmyetinated fibers(Ufs). Type II is recessively inherited and nerve biopsies show total absence of MFs but presence of Ufs. Type III is a recessive inherited dysautonomia. Type IV is characterized by insensitive to pain anhidrosis, and mild mental retardation with virtually absence of Ufs. Type V affects small MFs. We report a 5 year-old girl who presented with congenital insensitivity to pain, anhidrosis with mild mental retardation. In sural nerve biopsy, Ufs were virtually absent by electron microscopy. We reconfirmed previous pathologic findings in sural nerve of HSAN IV.

A Case of Hypokalemic Myopathy Associated with Bartter's Syndrome

Bartter's syndrome is characterized by hyperreninemia, hyperaldosteronism, hypokalemic hypochlorenlic alkalosis, normal blood pressure, juxtaglomerular apparatus hyperplasia, general weakness, and muscle weakness. We experienced a case of hypokalemic myopathy associated with Bartter's syndrome in 15 years old male. He had experienced paroxysmal muscle weakness without sensory change and myalgia since 10 years old. Subsequently, he had complaints of progressive muscle weakness, especially proximal muscles. Prominent juxtaglomerular apparatus with cellular proliferation biopsy was seen in the kidney. And there were mild perivascular inflammatory cell infiltration, small degenerating and/or regenerating muscles fibers, and normal muscle fiber distribution without evidence of chronic myopathy in the muscle biopsy. The patient was sucessfully managed with indomethacin and oral potassium chloride.

A Case of Multiple Brain Abscess associated with Bacterial Meningitis

Brain abscess consists of suppurative necrosis of the brain parenchyma. Young adult male often affected. Most abscesses arise from structures surrounding the brain: (middle ear, temporal bone, tonsil infection) about 40-50%. Metastatic bloodstream spread of infection from the SBE (subacute bacterial endocarditis) and lungs in adult or from remote sites, cyanotic congenital heart disease, and penetrating head trauma or brain surgery can also result in brain absecess. Multiple brain abscess associated with bacterial meningitis cases rarely reported in neonate s and young infants, but in adult case is not reported in Korea. We report a 61-year-old man who has multiple brain abscess associated with bacterial meningitis (Eschesrichia Coli).

A Clinical Study of Metastatic Spinal Epidural Tumor

The authors analysed 40 cases of metastatic spinal epidural tumor who admitted to the Wonju Christian hospital and Severance hospital, Yonsei University from January, 1989 to September, 1993. The results were summarized as follows: 1. The mean age was 54.7 years old and the metastatic spinal epidural tumor was most common in the 7th decade of age (35.0%). 2. The most common primary tumor was lung cancer (37.5%), and the rests were hepatoma (15.0%), leukemia (7.5%), stomach cancer (7.5%), lymphoma (5.0%) and pancreas cancer (5.0%), while 4 cases (10.0%) were of unknown primary tumor. 3. The level of the involved spine was thoracic (67.5%), lumbosacral (25.0%), and cervical (7.5%) in orders. 4. The most common initial symptom was pain and the common symptoms at diagnosis were pain, weakness, sensory loss and voiding difficulty. 5. In radiologic studies, plain X-ray showed bone involvement in 70.6%, 74.1% in bone scan and 87.5% in MRI respectively. 6. Signal intensity of tumor in MRI was iso or low on T1WI and high on T2WI. 7. Response to treatment was excellent in 60%, especially in early treated group within 5 days.

Therapeutic Trials in Two Cases with Chronic Meningitisvia Ommaya Reservoir

Ommaya reservoir implantation has been used for sterile assessment into ventricular CSF or direct chemotherapy of chronic meningitis and meningeal involvement of malignancy since 1963. We experienced two cases with chronic meningitis, one was tuberculous meningitis with obstructive hydrocephalus which was not improved by repetitive shunt and the other was cryptococcal meningitis which was not improved by traditional chemotherapy of intravenous amphotericin B and oral flucytosine. Ommaya reservoir was implanted for daily CSF drainage of intractable hydrocephalus in the first patient and for direct injection of amphotericin B into ventricle in the second patient. Both of two cases were successfully managed by the reservoir. Therefore, Ommaya reservoir could be useful in patients with chronic meningitis which are not improved by traditional management.

Balint Syndrome in a Patient with Sysemic Lupus Erythematosus-Scleroderma Overlap Syndrome

Balint syndrome is a rare cortical visual disorder in a patient with bilateral parieto-occipital lesions, which consists of psychic paralysis of visual fixation, optic ataxia and visual inattention. The most common cause of Balint syndrome is borderzone infarction and the other causes are gun-shot wounds, postpartum venous thrombosis, Creutzfeldt-Jakob disease, encephalopathy following eclampsia, human immunodeficiency virus encephalitis, and primary and metastatic brain tumor. We report a case of Balint syndrome which was caused by central nervous system involvement of systemic lupus erythematosus-scleroderma overlap syndrome, comfirmed by clinical features, irnmunologic and radiologic studies.